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ABSTRACT: To determine the feasibility of adjuvant paclitaxel and carboplatin chemotherapy interposed with involved field radiotherapy for women with advanced endometrial cancer.
This was a prospective cohort study of women with Stage III and IV endometrial cancer. Adjuvant therapy consisted of 4 cycles of paclitaxel (175 mg/m(2)) and carboplatin (350 mg/m(2)) every 3 weeks, followed sequentially by external beam radiotherapy (RT) to the pelvis (45 Gy), followed by an additional two cycles of chemotherapy. Para-aortic RT and/or HDR vault brachytherapy (BT) were added at the discretion of the treating physician.
Thirty-three patients (median age, 63 years) received treatment between April 2002 and June 2005. Median follow-up was 21 months. Stage distribution was as follows: IIIA (21%), IIIC (70%), IVB (9%). Combination chemotherapy was successfully administered to 30 patients (91%) and 25 patients (76%), before and after RT respectively. Nine patients (27%) experienced acute Grade 3 or 4 chemotherapy toxicities. All patients completed pelvic RT; 19 (58%) received standard 4-field RT and 14 (42%) received intensity-modulated radiotherapy. Ten (30%) received extended field radiation. Four patients (12%) experienced acute Grade 3 or 4 RT toxicities. Six (18%) patients developed chronic RT toxicity. There were no treatment-related deaths. Two-year disease-free and overall survival rates were both 55%. There was only one pelvic relapse (3%).
Adjuvant treatment with combination chemotherapy interposed with involved field radiation in advanced endometrial cancer was well tolerated. This protocol may be suitable for further evaluation in a clinical trial.
International Journal of Radiation OncologyBiologyPhysics 02/2007; 67(1):110-6. · 4.11 Impact Factor
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ABSTRACT: To determine if stratification of limited stage small cell lung cancer (LSCLC) patients by pre-treatment pulmonary function test (PFT) prognostic indicators predicts for treatment-related toxicity risks and survival following concurrent chemoradiation.
From 1989 to 1999, 215 LSCLC patients received six cycles of alternating cyclophosphamide/doxorubicin/vincristine and etoposide/cisplatin (EP). Thoracic radiation (RT) was initiated only with EP and at cycle 2 or 3. RT dose was: 40 Gy/15 fractions/3 weeks or 50 Gy/25 fractions/5 weeks. RT fields encompassed gross and suspected microscopic disease with a 2 cm margin. Pre-treatment PFT values analyzed included forced expiratory volume in 1s (FEV1) (in liter and as % predicted) and diffusion capacity for carbon monoxide (DLCO) (as % predicted). The "marker" for toxicity during concurrent chemoradiation was the duration of any RT breaks initiated for severe hematologic or locoregional symptomatology. Patient outcomes were analyzed for associations between recognized PFT cut-offs (FEV1 <2l, > or =2l; FEV1 <60%, > or =60% predicted; DLCO <60%, > or =60% predicted), toxicity rates, and survival.
For the whole study cohort, median, 2- and 5-year overall survivals were: 14.7 months, 22.7 and 7.2%, respectively. Fifty-six patients (26%) required treatment breaks due to toxicity. FEV1 and DLCO results were available for 96 (45%) and 86 (40%) patients, respectively. Two thirds of FEV1s measured were <2l. On statistical analysis, the incidence of toxicity-related interruptions was significant for DLCO<60% (P=0.043), suggestive for FEV1<2l (P=0.1) and non-significant for FEV1<60%. Patients with simultaneous DLCO<60% and FEV1<2l showed a trend toward increase toxicity risk (P=0.1). For selected PFT measures, median overall survivals were: 12.7 months versus 14.8 months for DLCO<60% versus > or =60%; 13.4 months versus 17.7 months for FEV1<2l versus > or =2l; 15.4 months versus 19.9 months for DLCO<60% + FEV1<2l versus DLCO> or =60% + FEV1> or =2l. Although absolute differences favored all patients with PFT values above the prognostic cut-offs, differences were not statistically significant on this analysis. Patients with both a treatment break and a DLCO<60% had the poorest median survival of all patient subsets, at 11.4 months (P=0.09).
Impaired DLCO (i.e. <60%) is a novel predictor of increased treatment-related toxicity leading to interruptions. The present study suggests a probable role for DLCO and FEV1 (in l) as prognostic factors for predicting survival but larger patient samples are required for confirmation. Patients with impaired DLCOs experiencing treatment interruptions have the poorest survival. Assessment of pre-treatment PFTs contributes to determining optimal management strategies for LSCLC patients receiving definitive chemoradiation.
Lung Cancer 02/2004; 43(2):159-66. · 3.43 Impact Factor
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ABSTRACT: The goal of this study was to ascertain the first cycle intolerability rate of the standard Mayo Clinic regimen, 5-fluorouracil (5-FU) 425 mg/m2 with low-dose folinic acid (FA) 20 mg/m2, as a rapid bolus intravenous injection (5-FU/FA) for 5 days every 4-5 weeks for advanced colorectal cancer chemotherapy. The 5-FU/FA arms of 2 large, randomized, controlled trials of 5-FU/FA versus raltitrexed, performed in Europe and North America, were analyzed for intolerability. Two hundred and twelve European patients and 200 North American patients with locally advanced or distant metastatic colorectal cancer were assigned to the Mayo Clinic regimen. During cycle 1, intolerability of the therapy was assessed. Intolerability was recognized as a protocol-driven, toxicity-mandated dose reduction in cycle 2, the inability to complete 5 days of cycle 1 due to toxicity, or failure to receive cycle 2 at all because of toxicity. After the first cycle of chemotherapy, the intolerability rate for the European trial was 41.0% (95% confidence interval [CI], 34.3-47.6) and 49.0% (95% CI, 42.0-56.0) for the North American trial. For the combined 5-FU/FA populations, the intolerability rate was 44.8% (95% CI, 40.0-49.7). The predominant toxicities were stomatitis, diarrhea, and leukopenia. The standard Mayo Clinic regimen was associated with a higher level of dose-limiting toxicities than the accepted maximum of up to 33% for standard chemotherapy.
Clinical Colorectal Cancer 09/2002; 2(2):111-8. · 1.68 Impact Factor
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ABSTRACT: This study is a retrospective analysis of thymidylate synthase (TS) levels in patients with stage II (T3 or T4) and III colon cancer. Two groups of patients were identified: one undergoing surgery alone (98 patients) and the second receiving adjuvant 5-fluorouracil chemotherapy (112 patients). TS analyses were carried out using the 106 monoclonal antibody and a published grading system dividing staining into high and low intensity. The distribution of patients with low versus high TS levels was similar in the two groups. There was no association between TS staining intensity and grade, stage or location of primary. Seventy-nine patients have relapsed: 46 (48%) in the surgery only group, 33 (30%) in the adjuvant therapy group (median follow-up: 51 and 61 months). Similar proportions relapsed when analyzed according to TS: in the surgery only group, 41% of patients with low TS, 48% with high TS; in the adjuvant group, 31% with low TS, 30% with high TS. In the surgery only group, a trend toward improved disease-free survival (DFS) was seen in the low TS group (84 versus 63% at 2 years, p = 0.08). No difference was seen in overall survival. There were no differences in DFS or overall survival in patients receiving adjuvant therapy according to TS intensity. The trend for worse outcome in patients with high TS is consistent with previous reports. The lack of difference in outcome for patients with low and high TS receiving chemotherapy suggests that high TS levels may predict greater benefit from adjuvant treatment.
American Journal of Clinical Oncology 11/2001; 24(6):597-602. · 2.01 Impact Factor
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ABSTRACT: Despite the perception that standard 5-fluorouracil/folinic acid (5-FU/FA) (425 mg/m2 per day and 20 mg/m2 per day intravenously once daily × 5 every 4 or 5 weeks) is well tolerated, we have been impressed by toxicity seen and frequent need for dose modification. We performed a retrospective analysis to quantitate the proportion of patients experiencing toxicity and attempted to identify associated clinical characteristics. One hundred thirty-four patients received 5-FU/FA at standard doses described by the Mayo regimen. Patient characteristics were as follows: female 35%, median age 66 years, Eastern Cooperative Oncology Group performance status less than or equal to 2, 96%. Sixty-eight percent received chemotherapy for metastatic disease. Forty-seven patients (35% ± 8%) experienced significant toxicity and were unable to receive the second cycle as scheduled: 76% required dose reduction, 11% discontinued therapy (including two toxic deaths), 11% discontinued therapy during the first cycle, and 2% required dose delay. Logistic regression was used to explore the following as predictors of toxicity: age, sex, performance status, adjuvant versus metastatic setting, prior chemotherapy, prior radiation, mean corpuscular volume, red blood cell distribution width, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, and calculated creatinine clearance. No clinical characteristic was found to predict toxicity. Only high bilirubin approached statistical significance. We conclude that standard 5-FU/FA, when used in the general population, is associated with significant toxicity. Known clinical characteristics are not helpful in predicting toxicity. The lack of previous formal phase I evaluation of this regimen of 5-FU/FA raises concerns regarding its safety and generalizability in clinical practice.
American Journal of Clinical Oncology 01/2000; 23(1):94-98. · 2.01 Impact Factor
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ABSTRACT: To look for survival differences between men and women with limited stage small cell lung cancer (LS-SCLC) by examining stratified variables that impair treatment efficacy.
A retrospective review of 215 LS-SCLC patients treated from 1989 to 1999 with concurrent chemotherapy-radiotherapy modelled on the 'early-start' thoracic radiotherapy arm of a National Cancer Institute of Canada randomized trial.
Of 215 LS-SCLC patients, 126 (58.6%) were men and 89 (41.4%) were women. Smoking status during treatment for 186 patients (86.5%) was: 107 (58%) nonsmoking (NS) (76 [71%] male [M]; 31 [29%] female [F]) and 79 (42%) smoking (S) (36 M [46%]; 43 F [54%]) (continuing-to-smoke F versus M, P=0.001). Fifty-six patients (26%) had radiotherapy interruptions (RTI) during chemotherapy-radiotherapy because of toxicity. Radiotherapy breaks were not associated with sex (P=0.95). Survival by sex and smoking status at two years was: F + NS = 38.7%; F + S = 21.6%; M + NS = 22.9%; and M + S = 9.1% (P=0.0046). Survival by sex and RTI status at two years was: F + no RTI = 32.4%; F + RTI = 23.6%; M + no RTI = 23.0%; and M + RTI = 3.8% (P=0.0025). Diffusion capacity for carbon monoxide (DLCO) was recorded for 86 patients (40%) and median survival by sex and DLCO was F = 16.7 months and M = 12.1 months for a DLCO less than 60%; and for a DLCO 60% or more, F = 15.1 months and M = 15.3 months. First relapses were recorded in 132 cases (61%), with chest failure in men (45%) greater than for women (35%) and cranial failure rates similar between sexes (48%). Upon multivariable analysis, continued smoking was the strongest negative factor affecting survival.
In LS-SCLC, women overall do better than men, with or without a negative variable. The largest quantifiable improvement in survival for women came from smoking cessation, and for men from avoidance of breaks during treatment.
Canadian respiratory journal: journal of the Canadian Thoracic Society 12(5):245-50. · 1.56 Impact Factor
