Clinical Evaluation of Procarbazine and Fluorouracil in Advanced Lung Cancer

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Abstract
Procarbazine and 5-fluorouracil were given to 69 untreated patients with inoperable or metastatic lung cancer. 62 were adequately evaluable. The patients were divided into 3 groups: A) 26 cases received procarbazine (250 mg/day i.v. for 4 weeks); B) 24 cases received procarbazine in association with 5-fluorouracil given by rapid single i.v. injection (10 mg/kg on alternate days for 4 weeks); C) 12 cases received procarbazine in association with 5-fluorouracil which was given by 2 hour i.v. infusion on alternate days for 4 weeks. No maintenance treatment was given. The objective responses were evaluated following the categories of Karnofsky. Considering only the category 1 responses, 15 % of patients of group A showed objective improvement, in comparison to 43 % and 16 % of patients of group B and C respectively. Therefore, it seems that the combination of procarbazine and 5-fluorouracil (rapid i.v. injection) is better than procarbazine alone, and that the combined treatment is more successful when 5-fluorouracil is given by single i.v. injection rather than through slow i.v. infusion. Regressions were observed in all histologic types. However, in the group of cases with adenocarcinoma none (0/5) responded to procarbazine alone but 5/6 to procarbazine plus 5-fluorouracil. It is likely that procarbazine is more effective in the oat-cell type and 5-fluorouracil in adenocarcinomas. Toxicity consisted in nausea and vomiting during the first 7–10 days in the group treated with procarbazine alone (15/26 cases), while only 2/26 patients had transient leukopenia. In group B the side-effects were diarrhea (13 cases) and leukopenia (9 cases), both possibly due to 5-fluorouracil. Only 2/12 patients of group C showed side-effects (1 vomiting and 1 diarrhea). The fact that no patients of this group showed signs of bone marrow depression confirms what is already known, i.e. that when 5-fluorouracil is given by slow i.v. infusion toxicity rarely occurs. The conclusion is that the association of procarbazine with 5-fluorouracil can produce consistent regressions in patients with advanced carcinoma of the lung, although unmaintained remissions are almost always short lived.