Paclitaxel and simultaneous radiation in the treatment of stage IIIA/B non-small cell lung cancer.

In a clinical phase II trial, escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) were given with concurrent radiation to patients with stage IIIA/B non-small cell lung cancer. Radiotherapy was given in daily doses of 2 Gy, 5 days a week, in weeks 1 through 3 and 6 through 8. Paclitaxel was given on day 1 of weeks 1 through 3 and 6 through 8, at a starting dose level of 50 mg/m2. Subsequent paclitaxel dose levels were 60, 72, 86, and 103 mg/m2. Three to six patients were included at each dose level until intolerable toxicity (World Health Organization grade 3 or 4 leukopenia) occurred in three of six patients. To date, 27 patients have entered the protocol. Hematologic toxicity was mild with no severe myelosuppression up to the 86-mg/m2 dose level. At paclitaxel 103 mg/m2, four of six patients developed grade 3 or 4 leukopenia, and dose escalation was stopped. The maximum tolerated dose was thus determined to be 86 mg/m2. The main clinical toxicity was the occurrence of pulmonary infections (seven patients), one of whom had Pneumocystis carinii infection; the six others had interstitial infections with no pathogen isolated. Mild to moderate esophagitis was seen in five patients. Thus far, of 24 patients evaluable for response, 18 showed decreased tumor size. Four patients achieved major responses (near-complete disappearance of radiologic tumor signs), 11 patients achieved partial remission, and three patients had a minor response. The overall response rate was 75%. In summary, the maximum tolerated dose of paclitaxel in this study has been determined to be 86 mg/m2 weekly. Pulmonary infections represent the major clinical toxicity, and the high response rate merits further clinical evaluation of this regimen.

Paclitaxel and simultaneous radiation in the treatment of stage III A/B non-small cell lung cancer.

In a clinical phase II trial, radiotherapy and escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) were given concurrently to patients with stage IIIA/B non-small cell lung cancer. Radiotherapy was given in daily doses of 2 Gy, 5 days a week, in weeks 1 to 3 and 6 to 8 for a total dose of 56 Gy. Paclitaxel was given in 3-hour infusions on day 1, also in weeks 1 to 3 and 6 to 8. The starting dose level was 50 mg/m2; the subsequent dose levels were 60, 72, 86, and 103 mg/m2. Cohorts of three to six patients were assigned to each dose level until intolerable toxicity (eg, World Health Organization grade 3 or 4 leukopenia) occurred in three of the six patients. Currently, 15 patients have entered the study. Twelve patients have finished the treatment protocol and are evaluable for toxicity and response. Hematologic toxicity was mild, and even at 86 mg/m2, the highest evaluable dose level, no severe myelosuppression was noticed. The main clinical toxicity was the occurrence of pulmonary infections, which were seen in five patients. One of these patients had a Pneumocystis carinii infection, but no pathogens were isolated from the four others with interstitial infections. Mild to moderate esophagitis was seen in five patients. All patients showed a decrease of tumor size. Four patients had a major response with nearly complete disappearance of radiologic tumor signs, five patients had a partial remission, and three patients experienced a minor response. Thus, the overall response rate was 75%. In summary, the maximum tolerated dose of paclitaxel has not yet been achieved, the occurrence of pulmonary infections represents the major clinical toxicity, and the extremely high response rate merits further clinical evaluation of this regimen.