ABSTRACT
OBJECTIVES: This study was performed to evaluate the addition of temozolomide (TMZ) to whole brain radiotherapy (WBRT) for brain metastases from melanoma. METHODS: Seven patients with brain metastases from melanoma were treated on a North Central Cancer Treatment Group (NCCTG) trial (N0274) of TMZ plus WBRT. TMZ was given orally in doses of 200 mg/m² for 5 days every 4 weeks for up to 8 cycles. WBRT was started on the first day of TMZ and included the delivery of 3750 cGy in 15 fractions. In addition, separately analyzed was a cohort of 53 patients treated at the Mayo Clinic who received WBRT alone (39 patients) or WBRT plus TMZ (14 patients). RESULTS: The median survival of the 7 patients treated on N0274 was 3.6 months with 2 of 7 (29%) failing in brain and 5 of 7 (71%) failing elsewhere. For the other cohort of 53 patients, the median survival was 3.8 months with WBRT alone compared 4.3 months for WBRT plus TMZ (P = 0.5). CONCLUSIONS: Patients did not appear to benefit from the addition of TMZ to WBRT for the treatment of their brain metastases. Further improvements in outcome will require research to discover more effective systemic therapy and RT techniques.
Subject(s)
Brain Neoplasms/secondary , Brain Neoplasms/therapy , Cranial Irradiation/methods , Dacarbazine/analogs & derivatives , Melanoma/secondary , Melanoma/therapy , Skin Neoplasms/pathology , Administration, Oral , Aged , Antineoplastic Agents/administration & dosage , Brain Neoplasms/mortality , Cohort Studies , Combined Modality Therapy , Dacarbazine/administration & dosage , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Melanoma/mortality , Middle Aged , Radiotherapy Dosage , Retrospective Studies , Risk Assessment , Skin Neoplasms/mortality , Skin Neoplasms/therapy , Survival Analysis , Temozolomide , Treatment OutcomeABSTRACT
PURPOSE: To determine the maximum tolerated dose (MTD) and efficacy of pemetrexed and gemcitabine in patients with either biliary tract or gallbladder carcinoma. PATIENTS AND METHODS: Patients with unresectable previously untreated biliary tract cancers were eligible for participation. An initial phase I trial was performed to determine the MTD using an every-2-weeks schedule. The MTD was then used in the phase II portion of the trial. The primary end point for the phase II portion was 6-month survival with a planned accrual of 59 patients. RESULTS: Overall, 63 eligible patients were enrolled. The MTD was established as pemetrexed 500 mg/m2 IV over 10 min and gemcitabine 800 mg/m2 IV at 10 mg/m2 per minute on days 1 and 15 of an every-4-weeks schedule with vitamin B12 and folate supplementation. Fifty-eight patients were included in the phase II portion. Median age was 61 and median follow-up was 18.2 months. A median of three cycles of treatment was given. Six-month survival was 55% and the median survival was 6.6 months (95% confidence interval 5.4-8.7 months) with a median time to progression of 3.8 months (2.4-5.4). Forty-seven (81%) experienced at least one grade 3+ adverse event, and 28 patients (48%) experienced at least one grade 4 adverse event, most of which were due to grade 4 neutropenia. CONCLUSION: The addition of pemetrexed to fixed-dose-rate gemcitabine, in a biweekly schedule, did not enhance the activity of gemcitabine in patients with biliary tract or gallbladder carcinoma.
