Chemoradiotherapy comparing different chemotherapeutic agents: Three randomized trials of chemoradiotherapy evaluated different chemotherapeutic agents (Table 1[C]). The Southwest Oncology Group randomly allocated 69 patients to 60 Gy of radiation with methyl lomustine 125 mg/m2 orally every six weeks and 5-FU 400 mg/m2 weekly, with or without testalactone 200 mg orally daily. Survival was similar in each arm (P=0.68). Among 62 evaluable patients, the most common adverse effects were myelosuppres-sion (87%) and gastrointestinal toxicity (23%), and there was one treatment-related death associated with granulocytopenia.
In 1988, the GITSG reported a randomized controlled trial evaluating multidrug chemotherapy with streptozocin 1 g/m2 day 1, mitomycin-C 10 mg/m2 day 1, and 5-FU 600 mg/m2 (SMF) on days 1, 8, 29, and 36 given in eight-week cycles for two years, or until disease progression, versus 54 Gy of radiation given with 5-FU 350 mg/m2/day on the first three and last three days of radiotherapy. According to the Nominal Standard Dose concept of Orton and Ellis, the single course of 54 Gy was considered to be radiotherapeutical-ly equivalent to the 60 Gy double-split regimens used in earlier studies by the GITSG. Following radiation, patients were given SMF for up to two years. The study was closed early due to lack of funding with only 24 patients in each arm. Overall survival was significantly better with combined-modality treatment (median survival 42 weeks, 41% at one year) compared with chemotherapy alone (median survival 32 weeks, 19% at one year) (P<0.02). At 18 months, 18% of patients in the combined-modality arm were alive, but none were alive in the SMF-only arm. Severe toxicity was experienced by 50% of patients in the chemoradiotherapy group, with life-threatening leucopenia in four patients and life-threatening thrombocytopenia in one patient. There were no life-threatening adverse effects in the SMF-only arm. The GITSG results have been questioned because the study closed after accruing only 24 patients in each arm due to lack of funding. Therefore, any observed difference could be attributed to a statistical power issue caused by inadequate accrual, not any treatment effect.
TABLE 1 Randomized trials in locally advanced pancreatic cancer
|Reference||Radiation(Gy)||Chemotherapy||Number of patients randomized (evaluable)||Median Survival (months)||Percentage one-year survival (estimate*)|
|C) Chemoradiotherapy with comparison of different chemotherapy regimens|
|SWOG,||60||mCCNU+5-FU||NR (33)||8.8||NR (40)|
|1980||60 mCCNU+5-FU+testolactone||NR (29)||6.9||NR (27)|
|GITSG 9277,||60||5-FU||79 (73)||8.5||NR (33)|
|1985||40||doxorubicin||78 (70)||7.6||NR (26)|
|Earle et al,||50-60||5-FU||44 (44)||7.8||NR (34)|
|1994||50-60||Hycanthone||43 (43)||7.8||NR (26)|
*Calculated from survival curve where data not provided in the text; Tp<0.05. 5-FU Bolus 5-fluorouracil; ECOG Eastern Cooperative Oncology Group; GITSG Gastrointestinal Tumor Study Group; Gy Gray; mCCNU Methyl lomustine; NR Not reported; RTOG; Radiation Therapy Oncology Group; SMF Streptozocin, mitomycin, 5-FU; SWOG Southwest Oncology Group
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