We compared the effectiveness of fluorouracil (5-FU) alone (arm A), high-dose leucovorin plus 5-FU (arm B), and sequential methotrexate, 5-FU, and leucovorin (arm C) for treatment of patients with advanced colorectal carcinomas who had not received prior chemotherapy. Arm A consisted of infusions of 5-FU at 12 mg/kg/d intravenously (IV) for 5 days followed by weekly infusions of 5-FU at 15 mg/kg; arm B consisted of leucovorin infusions at 200 mg/m2/d IV plus infusions of 5-FU at 400 mg/m2/d IV on days 1 through 5 of a 28-day cycle; arm C consisted of methotrexate at 50 mg/m2 orally every 6 hours for five doses followed by infusions of 5-FU, 500 mg/m2 IV, and leucovorin, 10 mg/m2 orally, every 6 hours for five doses every other week. A total of 265 patients were entered into the trial, of whom 249 (94%) were fully evaluable. The objective response rate (complete [CR] plus partial [PR] responses) was 17.3% on arm A, 18.8% on arm B, and 19.8% on arm C (log-rank test, P greater than .4). The median time to failure was 138 days on arm A, 166 days on arm B, and 182 days on arm C (log-rank test, P values of arm A v B = .06; arm A v arm C = .04). Median survival was 345 days on arm A, 324 days on arm B, and 356 days on arm C (log-rank test, P greater than .4). Treatment with 5-FU alone was significantly more dose intensive and more toxic than either of the experimental combinations. The rates of grade 3 or greater nonhematologic toxicity were 42.3% on arm A, 24.3% on arm B, and 14.3% on arm C. Hematologic toxicity was milder but had the same pattern. This study indicates that these regimens of high-dose leucovorin plus 5-FU and sequential methotrexate, 5-FU, and leucovorin are not more effective than is 5-FU alone for treatment of patients with colorectal carcinomas when 5-FU is administered at high-dose intensity.

Sixty-five patients with nonmetastatic (Stages I, 11, and 111) esophageal cancer (EC) were treated with radiotherapy (RT) alone (56.00 to 61.00 Gy in 6 to 7 weeks) or synchronous combinations of radiotherapy and chemotherapy (RT-CT). RT-CT consisted of 41.40 to 50.40 Gy in 4.5 to 8 weeks with continuous infusion 5-fluorouracil 5-FU (1000 mg/m2/d for 4 days in weeks 1, 4, and 8), mitomycin C (10 mg/m2 intravenously [IV] in weeks 1 and 8), cisplatin (75 mg/m2 IV in week 4). Maintenance CT consisted of methotrexate (200 mg/m2 IV), leucovorin (10 mg/m2 orally every 6 hours for 5 doses), and 5-FU (600 mg/m2 IV) in weeks 10, 12, and 14. Thirty-five patients treated by RT alone (Group A) were comparable in terms of age, sex, AJC staging, histologic condition, and location of primary with 30 patients treated by RT-CT (Group B). In Group A (range, 2-to 144f months), two patients (42 and 144 months) are alive and well. In Group B (range, 2-to 59+ months), 12 patients (7 to 59 months) are alive and well. Median survival in Group A is 8 months, compared with 15 months for patients achieving a complete response (CR) in Group B. Patients in Group B achieved a 77% CR rate by endoscopy-biopsy, whereas 30% of the patients in Group A achieved a CR (P = 0.0001). The recurrence rates at the primary site/ regional nodes were 77% and 27% in Groups A and B, respectively (P = 0.0001). The incidences of distant metastases were 29% and 20%, respectively (P = 0.423). In Group A, the l-year and 2-year cumulative survival rates were 27% and 13%, respectively. In Group B, the cumulative survival rates were 53% at 1 year and 29% a t 2 years (P = 0.023). Aside from reversible myelotoxicity, the incidences of pulmonary fibrosis, esophagitis, and fistulae formation were less frequent in the combined technique treatment group. A compilation of reported chemoradiation protocols for EC indicates consistently improved l-year and 2-year survival rates, compared with surgical and RT series. The key to further improvement in the treatment of EC appears to lie in increasing the biologic response (RT fractionation and endocavitary RT) and optimal use of multiple effective C T agents with nonadditive toxicities.

Two hundred twenty‐three patients were enrolled on this randomized Phase III trial testing the value of late consolidative involved‐field radiation therapy in the treatment of limited‐stage small cell lung cancer (SCLC). Patients were treated with induction chemotherapy consisting of alternating cycles of procarbazine, vincristine, lomustine, and cyclophosphamide (POCC) and etoposide, doxorubicin, and methotrexate (VAM) for 6 to 9 months. Responding patients were then randomized at 6 or 9 months to chemotherapy alone or to involved‐field radiation therapy. All partial and complete responders received prophylactic cranial irradiation. Of the 180 eligible and evaluable patients, 80 (44%) achieved a complete response and 39 (22%) achieved a partial response (overall rate of response, 66%). Actuarial median survival time was 11.6 months, with 16% of patients surviving 2 years and 11% surviving 5 years. Forty‐eight patients were randomized to chemotherapy alone (24 patients) versus chemotherapy plus involved‐field radiation therapy (24 patients). There were no significant differences in time to progression or survival between those patients receiving or not receiving involved‐field radiation therapy. The thorax was the site of first relapse in 58% of patients randomized to chemotherapy alone versus 29% in patients randomized to chemotherapy plus involved‐field radiation therapy (P equals 0.042). The major acute toxicity was reversible myelosuppression, and the major late toxicity was chronic central nervous system dysfunction. The authors conclude that the addition of late consolidative radiation therapy to induction chemotherapy in the treatment of limited‐stage SCLC is well tolerated and improves local control, but does not improve time to progression or rates of survival.