Latest Articles Include:
- Physicians optimistic about advances in lung cancer and melanoma treatment
- Cancer 116(10):2287-2288 (2010)
- Shorter radiation treatments might equal or surpass traditional radiation
- Cancer 116(10):2289 (2010)
- Smoking decline reduces lung cancer disparity
- Cancer 116(10):2289 (2010)
- Central nervous system prophylaxis in adults with acute lymphoblastic leukemia : Current and emerging therapies
Jabbour E Thomas D Cortes J Kantarjian HM O'Brien S - Cancer 116(10):2290-2300 (2010)
Central nervous system (CNS) recurrence continues to be a significant complication in the treatment of adult patients with acute lymphoblastic leukemia (ALL). Preventing CNS recurrence has been a therapeutic challenge and has not been addressed critically in many clinical trials. Adult studies modeled on childhood ALL studies have used multiple treatment modalities, including radiation therapy, systemic therapy, intrathecal therapy, and combinations thereof. Cranial irradiation is effective but is offset by substantial toxicity, including neurologic sequelae. Systemic chemotherapy, especially with cytarabine (AraC) and methotrexate, has demonstrated promise in decreasing CNS recurrence, but therapeutic levels of drugs in the cerebrospinal fluid (CSF) are not maintained. Intrathecal chemotherapy with or without high-dose systemic therapy is the most common approach to CNS prophylaxis. Liposomal AraC recently has become available and confers prolonged levels of free AraC! in the CSF, a critical requirement for CNS prophylactic therapy. This review discusses the various modalities used for CNS prophylaxis in patients with ALL and the emerging trends, with specific emphasis on the outcome in terms of event-free survival and toxicity. Cancer 2010. © 2010 American Cancer Society. - A phase 2 study of a fixed combination of uracil and ftorafur and leucovorin given orally in a twice-daily regimen to treat patients with recurrent metastatic breast cancer
Hortobagyi GN Young RR Karwal M Ibrahim NK Hermann R Murray JL Watkins SP Gore I - Cancer 116(10):2301-2306 (2010)
BACKGROUND: UFT, a combination of uracil and ftorafur, was developed to combine the cytotoxic effects of 5-fluorouracil (5-FU) with convenient oral dosing. Leucovorin is combined with UFT to further potentiate the effect of 5-FU on tumor cells. Orally administered UFT and leucovorin provide higher peak plasma concentrations of 5-FU and prolonged therapeutic 5-FU concentrations compared with continuous infusion of 5-FU. METHODS: Ninety-four patients with metastatic breast cancer who had been previously treated with anthracyclines and/or taxanes were treated with UFT and leucovorin, given orally, for the first 28 days of a 35-day cycle. The total daily dose of UFT was 300 mg/m2, which was given in 2 divided doses every 12 hours. The primary endpoint was time to disease progression (TTP). Secondary objectives included overall tumor response rate (OR = complete response [CR] + partial response [PR]) and overall survival (OS). RESULTS: Of the 94 patients enrolled, 68 were evaluable for efficacy. Although no CRs were observed, 9 patients achieved PRs, for an OR of 13.2% in the evaluable population. The median TTP for the evaluable population was 10.3 weeks, and the proportion of patients free of disease progression at 6 months was 17%. The median OS was 61.6 weeks for all patients enrolled. The most common drug-related grade 3 adverse events (graded using the National Cancer Institute Common Toxicity Criteria version 2) were diarrhea, asthenia, nausea, and dehydration. CONCLUSIONS: The combination of UFT and leucovorin administered orally in a twice-daily regimen was found to have modest activity. Grade 3 toxicities were manageable with appropriate dose adjustments in patients with metastatic breast cancer previously treated with anthracyclines and/or taxanes. Cancer 2010. © 2010 American Cancer Society. - Excellent outcomes with adjuvant toremifene or tamoxifen in early stage breast cancer
Lewis JD Chagpar AB Shaughnessy EA Nurko J McMasters K Edwards MJ - Cancer 116(10):2307-2315 (2010)
BACKGROUND: Fareston (toremifene) and tamoxifen, both selective estrogen receptor modulators, are therapeutically equivalent treatments for metastatic breast cancer. We hypothesized that toremifene as compared with tamoxifen given as adjuvant therapy for early stage breast cancer would result in equivalent survival with an improved side effect profile, therefore, providing superior therapeutic efficacy. METHODS: The North American Fareston versus Tamoxifen Adjuvant trial assigned 1813 perimenopausal or postmenopausal women with hormone receptor (HR)-positive invasive breast cancer to adjuvant treatment with either tamoxifen or toremifene. The primary outcomes evaluated were disease-free survival (DFS) and overall survival (OS). RESULTS: Median follow-up was 59 months. The baseline characteristics of the 2 treatment groups were well-balanced. On the basis of intent-to-treat, 5-year actuarial DFS was not significantly different between tamoxifen and toremifene (91.2% [standard error of the mean [SE] 1.2%] vs 91.2% [SE 1.1%], respectively). Similarly, 5-year actuarial OS was not significantly different between tamoxifen and toremifene (92.7% [SE 1.1%] vs 93.7% [SE 1.0%], respectively). Controlling for patient age, tumor size, and tumor grade, a Cox multivariate survival analysis found no difference between patients randomized to toremifene versus tamoxifen in terms of OS (OR = 0.951; 95% confidence interval [CI], 0.623-1.451, P = .951) or DFS (OR = 1.037; 95% CI, 0.721-1.491, P = .846). Adverse events were similar in the 2 groups. CONCLUSIONS: Women treated with adjuvant hormonal therapy enjoyed excellent DFS and OS. No significant differences were found between treatment with either tamoxifen or toremifene. Treatment of HR-positive patients with either tamoxifen or toremifene is appropriate. Cancer 2010. © 2010 American Cancer Society. - Trends in renal tumor surgery delivery within the United States
Dulabon LM Lowrance WT Russo P Huang WC - Cancer 116(10):2316-2321 (2010)
BACKGROUND: Most small renal tumors are amenable to partial nephrectomy (PN). Studies have documented the association of radical nephrectomy (RN) with an increased risk of comorbid conditions, such as chronic kidney disease. Despite evidence of equivalent oncologic outcomes, PN remains under used within the United States. In this study, the authors identified the most recent trends in kidney surgery for small renal tumors and determined which factors were associated with the use of PN versus RN within the United States. METHODS: A population-based patient cohort was analyzed using the Surveillance, Epidemiology and End Results cancer registry (SEER 1999-2006). The authors identified 18,330 patients ages 40 to 90 years who underwent surgery for kidney tumors 4 cm in the United States between 1999 and 2006. RESULTS: In total, 11,870 patients (65%) underwent RN, and 6460 patients (35%) underwent PN. The ratio of PN to RN increased yearly (P < .001), representing 45% of kidney surgeries in 2006 for small tumors. There were significant differences in the cohort of patients who underwent PN versus RN, including age, sex, tumor location, marital status, year of treatment, and tumor size. When adjusting for these variables, being a man, age 70 years, urban residence, smaller tumor size, and more recent treatment year were predictors of PN. CONCLUSIONS: Although the total numbers of PN procedures increased in the United States between 1999 and 2006, there remains a significant under use of PN, particularly among women, the elderly, and those living in rural locations. Further investigation will be required to determine the reasons for these disparities, and strategies to optimize access to PN need to be developed. Cancer 2010. © 2010 American Cancer Society. - Long-term neurologic and peripheral vascular toxicity after chemotherapy treatment of testicular cancer
Glendenning JL Barbachano Y Norman AR Dearnaley DP Horwich A Huddart RA - Cancer 116(10):2322-2331 (2010)
BACKGROUND: Testicular cancer is curable in the majority of men, and persisting treatment toxicity is a concern. The authors report a cross-sectional study of the long-term effects of chemotherapy (C) on neurologic function and development of Raynaud phenomenon. METHODS: Seven hundred thirty-nine patients who were treated between 1982 and 1992 gave consent to enter the study. Patients were classified according to the receipt of C (n = 384) or no C (n = 355). Patients completed a general health questionnaire and a quality-of-life form (the European Organization for Research and Treatment of Cancer Quality-of-Life C30 questionnaire with testicular module). Symptom scores of 3 or 4 were considered clinically significant. Patients were assessed in the clinic, and clinical history was used to diagnose Raynaud phenomenon (RP) and tinnitus. Examinations included peripheral nerve function testing for light touch and vibration sense. Five hundred seventy-seven patients underwent audiometry. RESULTS: On physician assessment, peripheral neuropathy and RP were more common after C (21.7% vs 9.1% [P<.001] and 20.3% vs 1.7% [P<.001], respectively). Similar results were obtained for symptom scores (12.5% vs 5.5% [P = .002] and 9.7% vs 3.7% [P<.001], respectively). On multivariate analysis, for peripheral neuropathy, the significant predictors were cisplatin dose, carboplatin dose, and age. For RP, the significant predictor was bleomycin. Significant differences in hearing thresholds were noted at 8000 hertz only and, on multivariate analysis, were related to age, cisplatin dose, and vincristine dose. Auditory symptom scores did not differ between groups. CONCLUSIONS: With long-term follow-up, peripheral neuropathy and RP remained detectable in approximately 20% of patients and caused significant symptoms in 10% of patients. Detectable effects on high frequency remained but caused little symptomatic problem. These effects persisted and were related to the cumulative chemotherapy dose. Cancer 2010. © 2010 American Cancer Society. - Pretreatment assessment of tumor enhancement on contrast-enhanced computed tomography as a potential predictor of treatment outcome in metastatic renal cell carcinoma patients receiving antiangiogenic therapy
Han KS Jung DC Choi HJ Jeong MS Cho KS Joung JY Seo HK Lee KH Chung J - Cancer 116(10):2332-2342 (2010)
BACKGROUND: Tumor vascularity is a potential predictor of treatment outcomes in metastatic renal cell carcinoma (mRCC), and contrast enhancement of tumors in computed tomography (CT) is correlated significantly with microvessel density. In this study, the authors investigated whether tumor enhancement in contrast-enhanced CT (CECT) is useful for predicting outcomes in patients with mRCC who are receiving antiangiogenic therapy. METHODS: Attenuation values were reviewed retrospectively on CECT images of all metastatic lesions in 66 patients from February 2007 to November 2008. All patients received a tyrosine kinase inhibitor (either sunitinib or sorafenib). Tumor response was evaluated on CECT studies every 12 weeks. The authors analyzed the association between contrast enhancement and treatment outcomes, including objective response, tumor size reduction rate, time to response, and time to progression. RESULTS: In 46 patients, 198 metastatic lesions were assessed. Tumor size was reduced in 140 lesions (70.7%) and was increased in 58 lesions (29.3%). The mean reduction in size was 23.8%. The overall mean time to response and the time to progression were 8.6 months and 16.4 months, respectively. In multivariate analyses, tumor enhancement and enhancement pattern were associated with objective responses (P = .003 and P = .028, respectively). In addition, tumor enhancement was associated with tumor size reduction (P = .004). In Cox proportional hazards models, only tumor enhancement was associated significantly with the time to size reduction and progression-free survival (P = .03 and P = .015, respectively). CONCLUSIONS: Tumor enhancement on CECT images was associated with treatment outcomes and was identified as a potential predictor of treatment outcomes after antiangiogenic therapy in patients with mRCC. Cancer 2010. © 2010 American Cancer Society. - Invasive carcinoma of the uterine cervix associated with pregnancy : 90 years of experience
Pettersson BF Andersson S Hellman K Hellström AC - Cancer 116(10):2343-2349 (2010)
BACKGROUND: This study is a representation of 90 years of experience with carcinoma of the uterine cervix in pregnancy. The objective was to retrospectively study changes in the distribution of cervical carcinoma (CC) by age, disease stage, histopathology, survival, and the development of second primary cancers. METHODS: Altogether, 18,474 women with newly diagnosed CC were examined and treated at the Radiumhemmet between 1914 and 2004, including 9247 women who were of a childbearing age (<50 years) and 219 women who were pregnant. RESULTS: The mean patient age declined from 35 years (during 1914-1943) to 32.2 years (during 1960-2004). Similarly, the age range changed from ages 23 to 51 years (during 1914-1943) to ages 21 to 47 years (during 1960-2004). The relative incidence for all women aged <50 years who were treated for CC dropped considerably from 4.2% (during 1914-1943) to 1.2% (during 1960-2004), which translated into a reduction of by approximately 66%. At the time of diagnosis, stage I CC was observed in 75.6% of patients during 1960 to 2004 compared with 24.8% of patients during 1914 to 1943. The 10-year actuarial survival rate improved significantly during the study period from 27% (1914-2004) to 79% (1960-2004). The 10-year cause-specific cumulative actuarial survival rate for 41 women who were treated during 1960 to 2004 did not differ statistically from the rate for an age-matched, stage-matched, and histopathology-matched control series from the total cohort of women with CC who were treated at ! the Radiumhemmet during the same period (log-rank test; P = .85). CONCLUSIONS: During the study period, the incidence of CC during pregnancy declined, the cases were discovered at earlier stages, and survival improved. Furthermore, there was no increase in second primary cancers, and pregnancy did not appear to influence prognosis. Cancer 2010. © 2010 American Cancer Society. - Association of p53 codon 72 polymorphism with risk of second primary malignancy in patients with squamous cell carcinoma of the head and neck
Li F Sturgis EM Chen X Zafereo ME Wei Q Li G - Cancer 116(10):2350-2359 (2010)
BACKGROUND: p53 plays a critical role in cellular anticancer mechanisms, and has been correlated with second primary malignancy (SPM) development. A common polymorphism in codon 72 of p53 results in an amino acid substitution and could influence p53 function. The authors hypothesized that p53 codon 72 polymorphism may be associated with risk of SPMs and SPM-free survival among patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: A total of 1271 patients, who were diagnosed with incident SCCHN between May 1995 and January 2007, were genotyped and observed for SPM development. Log-rank test and Cox proportional hazard models were used to compare SPM-free survival and SPM risk between the different genotype groups. RESULTS: The authors found significantly reduced SPM-free survival for patients with variant proline (Pro) 72 allele compared with patients with arginine (Arg) 72 homozygous genotype (log-rank test, P = .005). Compared with SCCHN patients with the p53 72Arg/Arg genotype, there was a significantly greater risk of SPM associated with the p53 72Arg/Pro genotype (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.17-2.61) and combined p53 72Arg/Pro + Pro/Pro (HR, 1.58; 95% CI, 1.07-2.34). Furthermore, stratification analyses showed that the risk of SPM associated with p53 variant genotypes (Arg/Pro + Pro/Pro) was more pronounced in several subgroups. CONCLUSIONS: p53 codon 72 polymorphism could be a risk marker for genetic susceptibility to SPM in patients with primary SCCHN. Cancer 2010. © 2010 American Cancer Society. - Alemtuzumab by continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of patients with chronic lymphocytic leukemia recurrence
Faderl S Ferrajoli A Wierda W O'Brien S Lerner S Keating MJ - Cancer 116(10):2360-2365 (2010)
BACKGROUND: Monoclonal antibodies may be used more effectively in combination. A previous study of intravenous (iv) bolus alemtuzumab plus rituximab in patients with chronic lymphocytic leukemia (CLL) recurrence produced a response rate of 54% after a 4-week treatment period. METHODS: To optimize dose, schedule, and route of alemtuzumab, a study was designed exploring continuous intravenous infusion (civ) followed by subcutaneous (sc) alemtuzumab together with weekly iv rituximab in patients with previously treated CLL. RESULTS: Data from 40 patients with a median age of 59 years, and a median of 3 prior regimens (range, 1-8 regimens) were evaluable. Approximately 64% of patients were fludarabine-refractory. Seven patients (18%) achieved a complete response (CR), 4 (10%) a nodular partial response (nPR), and 10 (25%) a partial response for an overall response rate of 53%. Of 11 major responses (CR, nPR), 8 occurred after cycle 1. Response rates were highest in blood (94%), followed by liver/spleen (82%), bone marrow (68%), and lymph nodes (51%). The combination did not generate unexpected toxicities. Cytomegalovirus (CMV) reactivations occurred in 6 patients (15%) and responded well to anti-CMV therapy. High titers of anti-idiotype antibodies after sc alemtuzumab were demonstrated in 1 patient, but remained without clinical sequelae. CONCLUSIONS: The combination of civ/sc alemtuzumab plus rituximab has activity in some patients with recurrent/refractory CLL and maximum response is achieved after 1 cycle (4 weeks) in 73% of patients. Further exploration in other settings of CLL together with accompanying pharmacokinetic studies is recommended. Cancer 2010. © 2010 American Cancer Society. - Characteristics of pericardial effusions in patients with leukemia
Sampat K Rossi A Garcia-Gutierrez V Cortes J Pierce S Kantarjian H Garcia-Manero G - Cancer 116(10):2366-2371 (2010)
BACKGROUND: Little information exists regarding the prevalence and natural history of pericardial disease in patients with leukemia. Recently, it has been reported that the use of histone deacetylase inhibitors is associated with an increased incidence of pericardial effusions (PEs). To study the characteristics and treatment relationships of PEs in patients with leukemia, the authors retrospectively analyzed a cohort of patients with leukemia evaluated at a single center. METHODS: The authors reviewed 2592 patients with acute myeloid leukemia (AML, n = 1282, 49%), acute lymphocytic leukemia (ALL, n = 336, 13%), or myelodysplastic syndrome (MDS, n = 974, 38%), who were evaluated from August 2003 to July 2008. Electronic medical records were reviewed to select patients who had undergone at least 1 echocardiographic evaluation. Data regarding diagnosis, timing, effusion size, survival, and prior therapy were collected for the patients who had echocardiographic evidence of PEs. RESULTS: PEs were detected in 325 (20%) of the patients who had echocardiograms: 21% in AML, 23% in ALL, and 18% in MDS patients. Only a small portion of PEs were detected before the initiation of therapy: 26% in AML, 25% ALL, and 15% in MDS patients. Most PEs were of minimal size (70%) overall. No significant differences in effusion characteristics, including severity, were observed among different types of therapies. The presence of PEs had no impact on the survival of the patients evaluated. CONCLUSIONS: PEs are relatively common in patients with leukemia and do not appear to be related to specific types of therapy or to survival. Cancer 2010. © 2010 American Cancer Society. - Evaluation of the prognostic significance of Eosinophilia and Basophilia in a larger cohort of patients with myelodysplastic syndromes
Wimazal F Germing U Kundi M Noesslinger T Blum S Geissler P Baumgartner C Pfeilstoecker M Valent P Sperr WR - Cancer 116(10):2372-2381 (2010)
BACKGROUND: Lineage involvement and maturation arrest are considered to have prognostic significance in patients with myelodysplastic syndromes (MDS). However, although the prognostic value of neutropenia, thrombocytopenia, and monocytosis have been documented, little is known about the impact of eosinophils and basophils. METHODS: The authors examined the prognostic significance of eosinophils and basophils in 1008 patients with de novo MDS. Patients were enrolled from 3 centers of the Austrian-German MDS Working Group and were analyzed retrospectively. Blood eosinophils and basophils were quantified by light microscopy, and their impact on survival and leukemia-free survival was calculated by using Cox regression. RESULTS: Eosinophilia (eosinophils >350/L) and basophilia (basophils >250/L) predicted a significantly reduced survival (P < .05) without having a significant impact on leukemia-free survival. In multivariate analysis, eosinophilia and basophilia were identified as lactate dehydrogenase (LDH)-independent prognostic variables with International Prognostic Scoring System (IPSS)-specific impact. Although elevated LDH was identified as a major prognostic determinant in IPSS low-risk, intermediate-1 risk, and high-risk subgroups, the condition eosinophilia and/or basophilia was identified as a superior prognostic indicator in the IPSS intermediate-2 risk subgroup. CONCLUSIONS: The evaluation of eosinophils and basophils in patients with MDS was helpful and may complement the spectrum of variables to optimize prognostication in MDS. Cancer 2010. © 2010 American Cancer Society. - Phase 2 trial of pemetrexed disodium and carboplatin in previously untreated extensive-stage small cell lung cancer, N0423
Chee CE Jett JR Bernath AM Foster NR Nelson GD Molina J Nikcevich DA Steen PD Flynn PJ Rowland KM - Cancer 116(10):2382-2389 (2010)
BACKGROUND: In extensive-stage small cell lung cancer (SCLC), the combination of pemetrexed plus carboplatin has shown activity and appeared to be well-tolerated. We conducted a trial to confirm the efficacy and to assess the tolerability of this chemotherapy combination. METHODS: Patients with untreated extensive-stage SCLC were enrolled in this phase 2 open-labeled study. They receive pemetrexed 500 mg/m2 and carboplatin (area under the curve of 5) every 21 days for a maximum 6 cycles. The primary endpoint for this trial was the confirmed response rate and the accrual goal was 70 patients. RESULTS: Forty-six eligible patients (29 aged <70 years, 17 aged 70 years) were accrued to this study. The efficacy outcomes were similar between the 2 age groups. Overall, the confirmed response rate was 35% (16 of 46; 95% confidence interval [CI], 21%-50%), where all 16 were partial responses. On the basis of these results, we had strong evidence that the study would not meet the preset efficacy criteria and was, therefore, closed before full accrual. The median duration of response was 4.4 months (95% CI, 2.9-5.2). Median overall survival for patients aged <70 years and aged 70 years was 9.2 months (95% CI, 5.4-11.6) and 10.8 months (95% CI, 2.2-14.3), respectively. Grade 3 or higher toxicity rates were similar between the younger and older patients. Grade 3/4 and grade 4 hematological toxicities were observed in 46% and 26% of patients, respectively. CONCLUSIONS: Although well-tolerated, the combination of pemetrexed and carboplatin is not as effective as standard therapy in patients with untreated extensive-stage SCLC. Cancer 2010. © 2010 American Cancer Society. - Varying recurrence rates and risk factors associated with different definitions of local recurrence in patients with surgically resected, stage I nonsmall cell lung cancer
Varlotto JM Recht A Flickinger JC Medford-Davis LN Dyer AM Decamp MM - Cancer 116(10):2390-2400 (2010)
BACKGROUND: The objective of this study was to examine the effects of different definitions of local recurrence on the reported patterns of failure and associated risk factors in patients who undergo potentially curative resection for stage I nonsmall cell lung cancer (NSCLC). METHODS: The study included 306 consecutive patients who were treated from 2000 to 2005 without radiotherapy. Local recurrence was defined either as radiation (r-LR) (according to previously defined postoperative radiotherapy fields), including the bronchial stump, staple line, ipsilateral hilum, and ipsilateral mediastinum; or as comprehensive (c-LR), including the same sites plus the ipsilateral lung and contralateral mediastinal and hilar lymph nodes. All recurrences that were not classified as local were considered to be distal. RESULTS: The median follow-up was 33 months. The proportions of c-LR and r-LR at 2 years, 3 years, and 5 years were 14%, 21%, and 29%, respectively, and 7%, 12%, and 16%, respectively. Significant risk factors for c-LR on multivariate analysis were diabetes, lymphatic vascular invasion, and tumor size; and significant factors for r-LR were resection of less than a lobe and lymphatic vascular invasion. The proportions of distant (nonlocal) recurrence using these definitions at 2 years, 3 years, and 5 years were 10%, 12%, and 18%, respectively, and 14%, 19%, and 29%, respectively. Significant risk factors for distant failure were histology when using the c-LR definition and tumor size when using the r-LR definition. CONCLUSIONS: Local recurrence increased nearly 2-fold when a broad definition was used instead of a narrow definition. The definition also affected which factors were associated significantly with both local and distant failure on multivariate analysis. Comparable definitions must be used when analyzing different series. Cancer 2010. © 2010 American Cancer Society. - Phase 2 study of carboplatin, docetaxel, and bevacizumab as frontline treatment for advanced nonsmall-cell lung cancer
William WN Kies MS Fossella FV Liu DD Gladish G Tse WH Lee JJ Hong WK Lippman SM Kim ES - Cancer 116(10):2401-2408 (2010)
BACKGROUND: Bevacizumab has recently been demonstrated to prolong overall survival when added to carboplatin and paclitaxel for chemotherapy-naïve patients with nonsquamous nonsmall-cell lung cancer (NSCLC). However, the effects of combining bevacizumab with other standard, front-line, platinum-based doublets have not been extensively explored. We designed this single treatment arm, phase 2 trial to determine whether the combination of carboplatin, docetaxel, and bevacizumab is tolerable and prolongs progression-free survival of chemotherapy-naïve patients with advanced, nonsquamous NSCLC. METHODS: Forty patients were treated with up to 6 cycles of carboplatin (AUC 6), docetaxel (75 mg/m2), and bevacizumab (15 mg/kg) on Day 1 every 21 days. Patients with an objective response or stable disease received maintenance bevacizumab (15 mg/kg) every 21 days until disease progression. The primary endpoint was median progression-free survival. Secondary endpoints included safety, response rates, and overall survival. RESULTS: The median number of chemotherapy and maintenance bevacizumab cycles/patient was 6 and 2, respectively. Grades 3-5 adverse events included febrile granulocytopenia (10%), infections (13%), bleeding (13%), thrombotic events (13%), hypertension (5%), bowel perforation (5%), and proteinuria (3%). Median progression-free survival was 7.9 months and median overall survival was 16.5 months. Partial responses were observed in 21 patients (53%), and stable disease 6 weeks occurred in another 17 patients (43%), for a disease control rate of 95%. CONCLUSIONS: Carboplatin, docetaxel, and bevacizumab were feasible and effective for front-line treatment of advanced, nonsquamous NSCLC. These data provide further evidence that bevacizumab may be used in combination with multiple standard, platinum-based doublets in this setting. Cancer 2010. © 2010 American Cancer Society. - Weekly alternating therapy with irinotecan plus cisplatin and etoposide plus cisplatin in the treatment of patients with extensive small cell lung carcinoma
William WN Uyeki J Johnson FM Feng L Peeples BO Fossella FV Karp DD Blumenschein GR Stewart DJ Glisson BS - Cancer 116(10):2409-2415 (2010)
BACKGROUND: Irinotecan has significant activity in small-cell lung cancer (SCLC). The authors' previous phase 1 study of alternating weekly therapy with irinotecan/cisplatin (IP), etoposide/cisplatin (EP), and granulocyte-colony-stimulating factor (G-CSF) support was well tolerated and active in patients with SCLC. A phase 2 trial was conducted to estimate the efficacy of this regimen in previously untreated patients with extensive SCLC. METHODS: A total of 33 patients were treated between June 2002 and July 2007. Patients received 12 weeks of therapy with cisplatin (20 mg/m2) on Day 1 and irinotecan (100 mg/m2) on Day 1 and G-CSF on Days 2 to 5 (Weeks 1, 3, 5, 7, 9, and 11) followed by cisplatin (20 mg/m2) on Day 1 and etoposide (60 mg/m2) on Days 1 to 3 with G-CSF on Days 4 to 7 (Weeks 2, 4, 6, 8, 10, and 12). The primary endpoint was 1-year survival rate. RESULTS: Grade 4 neutropenia (toxicities were determined using the National Cancer Institute Common Toxicity Criteria [version 2.0]) was noted in 5 (1.5%) of 343 courses with neutropenic fever in only 5 (1%) of 343 courses. One patient died of neutropenic sepsis. Nonhematologic toxicities grade 2 were observed in 15 (4%) of 343 courses and were limited to fatigue, hyponatremia, and diarrhea. The overall objective response rate was 89% in 28 assessable patients (no complete responses and 25 partial responses). The median progression-free and overall survivals were 6.0 months and 10.9 months, respectively. The 1-year survival rate was 33%. CONCLUSIONS: Weekly therapy with IP alternating with EP and G-CSF support was well tolerated in patients with extensive SCLC, but did not demonstrate improved progression-free or overall survival when compared with historical controls at the study institution. Cancer 2010. © 2010 American Cancer Society. - Does MC1R genotype convey information about melanoma risk beyond risk phenotypes?
Kanetsky PA Panossian S Elder DE Guerry D Ming ME Schuchter L Rebbeck TR - Cancer 116(10):2416-2428 (2010)
BACKGROUND: A study was carried out to describe associations of MC1R variants and melanoma in a US population and to investigate whether genetic risk is modified by pigmentation characteristics and sun exposure measures. METHODS: Melanoma patients (n = 960) and controls (n = 396) self-reported phenotypic characteristics and sun exposure via structured questionnaire and underwent a skin examination. Logistic regression was used to estimate associations of high- and low-risk MC1R variants and melanoma, overall and within phenotypic and sun exposure strata. A meta-analysis of results from published studies was undertaken. RESULTS: Carriage of 2 low-risk or any high-risk MC1R variants was associated with increased risk of melanoma (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.0-2.8; and OR, 2.2; 95% CI, 1.5-3.0, respectively). However, risk was stronger in or limited to individuals with protective phenotypes and limited sun exposure, such as those who tanned well after repeated sun exposure (OR, 2.4; 95% CI, 1.6-3.6), had dark hair (OR, 2.4; 95% CI, 1.5-3.6), or had dark eyes (OR, 3.2; 95% CI, 1.8-5.9). We noted this same pattern of increased melanoma risk among persons who did not freckle, tanned after exposure to first strong summer sun, reported little or average recreational or occupational sun exposure, or reported no sun burning events. Meta-analysis of published literature supported these findings. CONCLUSIONS: These data indicate that MC1R genotypes provide information about melanoma risk in those individuals who would not be identified as high risk based on their phenotypes or exposures alone. Cancer 2010. © 2010 American Cancer Society. - Histology-specific nomogram for primary retroperitoneal soft tissue sarcoma
Ardoino I Miceli R Berselli M Mariani L Biganzoli E Fiore M Collini P Stacchiotti S Casali PG Gronchi A - Cancer 116(10):2429-2436 (2010)
BACKGROUND: This study was conducted to develop a histology-specific nomogram to predict postoperative overall survival (OS) at 5 and 10 years in primary retroperitoneal soft tissue sarcoma (STS). METHODS: Data registered at a single institution (National Cancer Institute, Milan, Italy) prospective sarcoma database were used. In the present analysis, patients with primary localized retroperitoneal STS resected with curative intent between 1985 and 2007 were included. A parametric piecewise exponential survival multivariate model was used for nomogram development, and internal validation was performed with standard methodologies. Known prognostic variables, such as age, tumor burden, histologic variant (as reviewed by a sarcoma pathologist), grade, and surgical margins were considered as putative predictors. RESULTS: Among the 192 patients analyzed, within 10 years from surgery, 114 patients were alive, with a median follow-up time of 55 months (interquartile range, 25-104 months). Among the investigated factors, only histologic subtype did not reach significance at the 10% level. The relative hazard increased while increasing tumor size up to about 25 cm, and decreased thereafter. CONCLUSIONS: A histology-specific nomogram for retroperitoneal STS is now available. It can be used for better assessing the risk of the single patient and then making individualized decisions within the specific subset of retroperitoneal sarcomas. Cross-check external validation should be performed. Cancer 2010. © 2010 American Cancer Society. - Do racial or socioeconomic disparities exist in lung cancer treatment?
Yang R Cheung MC Byrne MM Huang Y Nguyen D Lally BE Koniaris LG - Cancer 116(10):2437-2447 (2010)
BACKGROUND: Determine the effects of race, socioeconomic status, and treatment on outcomes for patients diagnosed with lung cancer. METHODS: The Florida cancer registry and inpatient and ambulatory data were queried for patients diagnosed from 1998-2002. RESULTS: A total 76,086 of lung cancer patients were identified. Overall, 55.6% were male and 44.4% were female. The demographic distribution of patients was 92.7% Caucasian, 6.7% African American, and 5.7% Hispanic. The mean age of diagnosis was 70 years old. African American patients presented at a younger age, with more advanced disease, and were less likely to undergo surgical therapy than their Caucasian counterparts. Median survival time (MST) for the entire cohort was 8.7 months, while MST for African American patients was 7.5 months. Patients who received surgery, chemotherapy, or radiation therapy demonstrated significantly improved outcomes. Stepwise multivariate analysis revealed that African American race was no longer a statistically significant predictor of worse outcomes once corrections were made for demographics and comorbid conditions, suggesting that the originally reported disparities in lung cancer outcomes and race may be in part because of poor pretreatment per! formance status. In contrast, patients of the lowest socioeconomic status continue to have a slightly worse overall prognosis than their affluent counterparts (hazard ratio = 1.05, P = .001). CONCLUSIONS: Lung cancer continues to carry a poor prognosis for all patients. Once comorbidities are corrected for, African American patients carry equivalently poor outcomes. Nonetheless, emphasis must be placed on improving pretreatment performance status among African American patients and efforts for earlier diagnosis among the impoverished patients must be made. Cancer 2010. © 2010 American Cancer Society. - Oxaliplatin and capecitabine in the treatment of patients with recurrent or refractory carcinoma of unknown primary site : A phase 2 trial of the Sarah Cannon Oncology Research Consortium
Hainsworth JD Spigel DR Burris HA Shipley D Farley C Macias-Perez IM Barton J Greco FA - Cancer 116(10):2448-2454 (2010)
BACKGROUND: Despite the widespread use of oxaliplatin-based regimens for colorectal and other gastrointestinal cancers, there is surprisingly little information regarding their empiric use for the treatment of carcinoma of unknown primary site (CUP). In the current study, the combination of oxaliplatin and capecitabine in patients with recurrent and refractory CUP was examined. METHODS: Patients with CUP who had received at least 1 previous chemotherapy regimen were treated with oxaliplatin (130 mg/m2 intravenously on Day 1) and capecitabine (1000 mg/m2 orally twice daily on Days 1-14). Treatment cycles were repeated every 21 days. Patients with objective response or stable disease after 2 cycles continued treatment for 6 cycles or until disease progression. RESULTS: Nine of 48 patients (19%) had objective responses to treatment; an additional 22 patients had stable disease at the time of first re-evaluation. After a median follow-up of 17 months, the median progression-free and overall survivals were 3.7 months and 9.7 months, respectively. This regimen was reasonably well tolerated by most patients. CONCLUSIONS: The combination of oxaliplatin and capecitabine was found to have activity as a salvage treatment for patients with CUP. This regimen should be considered in patients with clinical and pathologic features suggesting a primary site in the gastrointestinal tract. Further development of the regimen as a first-line therapy, or with bevacizumab added, is indicated. Cancer 2010. © 2010 American Cancer Society. - Medication errors involving oral chemotherapy
Weingart SN Toro J Spencer J Duncombe D Gross A Bartel S Miransky J Partridge A Shulman LN Connor M - Cancer 116(10):2455-2464 (2010)
BACKGROUND: Given the expanding use of oral chemotherapies, the authors set out to examine errors in the prescribing, dispensing, administration, and monitoring of these drugs. METHODS: Reports were collected of oral chemotherapy-associated medication errors from a medical literature and Internet search and review of reports to the Medication Errors Reporting Program and MEDMARX. The authors solicited incident reports from 14 comprehensive cancer centers, and also collected incident reports, pharmacy interventions, and prompted clinician reports from their own center. They classified the type of incident, severity, stage in the medication use process, and type of medication error. They examined the yield of the various reporting methods to identify oral chemotherapy-related medication errors. RESULTS: The authors identified 99 adverse drug events, 322 near misses, and 87 medical errors with low risk of harm. Of the 99 adverse drug events, 20 were serious or life-threatening, 52 were significant, and 25 were minor. The most common medication errors involved wrong dose (38.8%), wrong drug (13.6%), wrong number of days supplied (11.0%), and missed dose (10.0%). The majority of errors resulted in a near miss; however, 39.3% of reports involving the wrong number of days supplied resulted in adverse drug events. Incidents derived from the literature search and hospital incident reporting system included a larger percentage of adverse drug events (73.1% and 58.8%, respectively) compared with other sources. CONCLUSIONS: Ensuring oral chemotherapy safety requires improvements in the way these drugs are ordered, dispensed, administered, and monitored. Cancer 2010. © 2010 American Cancer Society. - A novel therapeutic combination for neuroblastoma : The vascular endothelial growth factor receptor/epidermal growth factor receptor/rearranged during transfection inhibitor vandetanib with 13-cis-retinoic acid
Zage PE Zeng L Palla S Fang W Nilsson MB Heymach JV Zweidler-McKay PA - Cancer 116(10):2465-2475 (2010)
BACKGROUND: High-risk cases of neuroblastoma have poor survival rates, and novel therapies are needed. Vandetanib (ZD6474, Zactima) is an inhibitor of the vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection (RET) tyrosine kinases, which have each been implicated in neuroblastoma pathogenesis. The authors hypothesized that vandetanib combined with 13-cis-retinoic acid (CRA), a differentiating agent used in most current neuroblastoma treatment regimens, would be effective against neuroblastoma tumor models. METHODS: The authors evaluated the effects of vandetanib with and without CRA on RET phosphorylation and on the proliferation and survival of human neuroblastoma cell lines in vitro. Using a subcutaneous mouse xenograft model of human neuroblastoma, they analyzed tumors treated with CRA, vandetanib, and the combination of vandetanib plus CRA for growth, gross and histologic appearance, vascularity, and apoptosis. RESULTS: Vandetanib treatment inhibited RET phosphorylation and resulted in induction of apoptosis in the majority of neuroblastoma cell lines in vitro, whereas CRA treatment induced morphologic differentiation and cell-cycle arrest. Treatment with vandetanib plus CRA resulted in more significant reduction in neuroblastoma cell viability than either alone. In a mouse xenograft model, the combination of vandetanib with CRA demonstrated significantly more growth inhibition than either alone, via both reduction in tumor vascularity and induction of apoptosis. CONCLUSIONS: Vandetanib induces neuroblastoma tumor cell death in vitro and reduces tumor growth and vascularity in vivo. The combination of vandetanib with CRA was more effective in reducing tumor growth than either treatment alone. The antitumor effects of vandetanib plus CRA suggest a novel combination for use in neuroblastoma patients. Cancer 2010. © 2010 American Cancer Society. - High-dose proton therapy and carbon-ion therapy for stage I nonsmall cell lung cancer
Iwata H Murakami M Demizu Y Miyawaki D Terashima K Niwa Y Mima M Akagi T Hishikawa Y Shibamoto Y - Cancer 116(10):2476-2485 (2010)
BACKGROUND: A study was undertaken to evaluate the clinical outcome of particle therapy for stage I nonsmall cell lung cancer (NSCLC). METHODS: From April 2003 to April 2007, 80 patients with stage I NSCLC were treated with proton therapy or carbon-ion therapy (57 with proton therapy and 23 with carbon-ion therapy) using 3 treatment protocols. In the first protocol, 80 gray equivalents (GyE) of proton therapy was given in 20 fractions, and the second proton therapy protocol used 60 GyE in 10 fractions. For carbon-ion therapy, 52.8 GyE was given in 4 fractions. After achieving promising preliminary results for the first protocol, the authors started to use the second proton therapy protocol to shorten the overall treatment time. Carbon-ion therapy was started in 2005, and thereafter, both proton and carbon-ion therapy plans were made for each patient, and the 1 that appeared superior was adopted. Patient age ranged from 48 to 89 years (median, 76 years). Thirty-seven patients were medically inoperable, and 43 refused surgery. Forty-two patients had T1 tumors, and 38 had T2 tumors. RESULTS: The median follow-up period for living patients was 35.5 months. For all 80 patients, the 3-year overall survival, cause-specific survival, and local control rates were 75% (IA: 74%; IB: 76%), 86% (IA: 84%; IB: 88%), and 82% (IA: 87%; IB: 77%), respectively. There were no significant differences in treatment results among the 3 protocols. Grade 3 pulmonary toxicity was observed in only 1 patient. CONCLUSIONS: Proton therapy and carbon-ion therapy are safe and effective for stage I NSCLC. Further investigation of particle therapy for stage I NSCLC is warranted. Cancer 2010. © 2010 American Cancer Society. - Pelvic radiotherapy and the risk of secondary leukemia and multiple myeloma
Wright JD St Clair CM Deutsch I Burke WM Gorrochurn P Sun X Herzog TJ - Cancer 116(10):2486-2492 (2010)
BACKGROUND: Although several studies had examined secondary malignancies in patients with specific primary tumor types, to the authors' knowledge there are very few data examining the long-term sequelae of pelvic radiation as a whole. The goal of the current study was to examine the risk of treatment-associated leukemia and multiple myeloma in patients treated with pelvic radiotherapy. METHODS: Patients with invasive tumors of the vulva, cervix, uterus, anus, and rectosigmoid treated from 1973 to 2005 and recorded in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patients were stratified based on receipt of pelvic radiotherapy. The incidence of secondary leukemia (except chronic lymphocytic leukemia) and multiple myeloma were examined. Multivariate Cox proportional hazards models and Kaplan-Meier curves were constructed to examine the association between pelvic radiation and the development of subsequent hematologic malignancies. RESULTS: A total of 199,268 individuals, including 66,896 (34%) who received pelvic radiotherapy and 132,372 (66%) not treated with radiation, were identified. In a Cox proportional hazards model adjusting for other risk factors, post-treatment leukemia was increased by 72% (hazard ratio [HR], 1.72; 95% confidence interval [95% CI], 1.37-2.15) in the patients who received pelvic radiotherapy. The risk of secondary leukemia peaked at 5 to 10 years after primary treatment (HR, 1.85; 95% CI, 1.40-2.44) and remained elevated even 10 to 15 years after initial treatment (HR, 1.50; 95% CI, 1.03-2.18). There was no significant association between radiation and the development of multiple myeloma (HR, 1.08; 95% CI, 0.81-1.44). CONCLUSIONS: Pelvic radiation was associated with an increased risk of secondary leukemia but did not appear to increase the risk of multiple myeloma. Cancer 2010. © 2010 American Cancer Society. - A note from history : The First Printed Case Reports of Cancer
Hajdu SI - Cancer 116(10):2493-2498 (2010)
Antonio Benivieni, an Italian physician, Theophilus Boneti, a Swiss physician, and Giovanni Battista Mogagni, an Italian physician, pioneered postmortem examination for finding hidden causes of diseases. By correlating the results of their clinical and postmortem examinations, they established the foundation of anatomic pathology, clinical medicine, and oncology. Cancer 2010. © 2010 American Cancer Society. - Divergent cancer pathways for early onset and late onset cutaneous malignant melanoma : A role for sex-site interaction
Pérez-Gomez B Aragonés N Pollan M - Cancer 116(10):2499 (2010)
Men and women with trunk melanoma have different age distributions. Age-specific rates in women suggest a possible role of female hormones in this location. - Reply to Divergent cancer pathways for early-onset and late-onset cutaneous malignant melanoma : A role for same-sex interaction
Anderson WF Tucker MA Rosenberg PS - Cancer 116(10):2500 (2010)
- Liver-intestine cadherin predicts microvascular invasion and poor prognosis of hepatitis B virus-positive hepatocellular carcinoma
Takamura M Aoyagi Y - Cancer 116(10):2501 (2010)
- Reply to Liver-intestine cadherin predicts microvascular invasion and poor prognosis of hepatitis B virus-positive hepatocellular carcinoma
Shi YH Ding ZB Fan J - Cancer 116(10):2501-2502 (2010)
- Erratum: Pathogenesis of osteoblastic bone metastases from prostate cancer
- Cancer 116(10):2503 (2010)
- Erratum: Proposed adjustments to pathologic staging of epithelial malignant pleural mesothelioma based on analysis of 354 cases
- Cancer 116(10):2503 (2010)
- Erratum: Progress for resectable cancer?: A population-based assessment of US practices
- Cancer 116(10):2503 (2010)
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