Phase I-II studies of oral tegafur (ftorafur).

A total of 65 patients with advanced colorectal or breast cancer were given oral tegafur in the phase I study. Of these, 28 patients had accurately measurable lesions and were entered into the phase II study. Patients with liver metastasis, compromised bone marrow, or a decreased oral intake to less than 50% of their normal intake were given a poor-risk schedule consisting of 0.75 g/m2/day divided into 4 doses/day X 28 day unless early toxicity developed. In the absence of any of the above deficits, patients were given a good-risk schedule of 1.25 g/m2/day X 21 days if no toxicity appeared. The courses were followed by a 2-3-wk rest period depending upon the speed to recovery from all reactions and then repeated. Compared with 5-FU, nausea and vomiting occurred more frequently with tegafur while hematologic toxicity was less common and less severe. The paucity of significant hematologic toxicity permitted courses of this drug to be given safely on an outpatient basis even to the point of slight reaction for optimal dosing. No serious reactions occurred in any of the 65 patients. The clinical results showed partial regressions in 6 of 21 colorectal cancer patients and 3 of 7 breast cancer patients. Six of the 9 responses occurred in patients who had previous 5-FU trials. The average duration of regression in the colorectal cancer patients on oral tegafur was 9 mo with a significantly increased survival of the responders.

Clinical results with megestrol acetate in patients with advanced carcinoma of the breast.

Since it has been clearly established that multiple drug chemotherapy is more effective than the use of a single drug for advanced carcinoma of the breast, the latter is not commonly used today. However, upon failure of one of two combinations of drugs, if any of these drugs are then tried singly they are rarely useful, and valuable time is lost. It is at this point that megestrol acetate, a potent progestin, was found to be effective in 30 per cent of a series of 161 patients with advanced carcinoma of the breast. This drug was given orally, 40 milligrams, after each meal and at bedtime, without any toxicity or any undesirable reactions, except a weight gain--not fluid retention--in patients less than 55 years of age. The average duration of response was 8.1 months from onset of megestrol acetate therapy and for the group classified as unchanged, 5.2 months. This drug is at least as effective as any steroid or cytotoxic compound but has the advantage of not producing toxicity and, with the exception of weight gain in patients less than 55 years, no undesirable reactions of any kind, such as bone marrow depression, alopecia, nausea, vomiting or diarrhea. Hence, it can be properly administered by the patient's physician or surgeon. Since oncologists known that medroxyprogesterone therapy had not shown promising use for advanced carcinoma of the breast, it was assumed that megestrol acetate also had little activity, and hence, it was not used. However, those who did give it a trial found it a valuable compound in the management of advanced carcinoma of the breast, even after failure of all hormonal or cytotoxic combination trials. It proved to serve as an important addition to our armamentarium in the management of advanced carcinoma of the breast.

A randomized trial to compare intravenous and oral etoposide in combination with cisplatin for the treatment of small cell lung cancer.

In a randomized multi-center study, 83 patients with small cell lung cancer were randomly assigned to treatment with cisplatin 100 mg/m2 intravenously (IV) day 1 and etoposide 120 mg/m2 IV days 1, 2, and 3 or cisplatin 100 mg/m2 IV day 1 and etoposide 120 mg/m2 IV day 1 and 240 mg/m2 orally days 2 and 3. Both regimens were repeated every 4 weeks. Prior to randomization, patients were stratified by extent of disease, performance status, and gender. A total of 41 patients were randomly assigned to the parenteral treatment only regimen, and 42 patients received cisplatin and IV/oral etoposide therapy. Both treatment arms were comparable regarding patient characteristics. Limited disease (LD) patients constituted 52% and 49% of the patient population for the oral and IV etoposide regimens, respectively. The overall complete response (CR) and partial response (PR) rate was 50% (95% confidence interval [CI] 35% to 65%) for the oral etoposide regimen and 59% (95% CI 44% to 74%) for the IV etoposide regimen (P = 0.438). For both regimens, 55% of the LD patients achieved either CR or PR. Time to progression and survival were comparable for both treatment arms. Hematologic toxicity was comparable in both treatment arms, with 80% of patients experiencing grade 3 or 4 neutropenia or thrombocytopenia. Moderate to severe anemia and weight loss were more predominant with the IV than with the oral regimen.