Results of a 2‐arm Phase II study of 9‐nitrocamptothecin in patients with advanced soft‐tissue sarcomas

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Abstract
BACKGROUND The authors conducted a 2‐arm Phase II trial of 9‐nitrocamptothecin (9‐NC), an oral topoisomerase I inhibitor, to define response rates in patients with gastrointestinal (GI) leiomyosarcomas and other soft‐tissue sarcomas (STS). METHODS Patients were required to provide informed consent and have measurable disease, Zubrod performance status ≤ 2, and adequate organ function. 9‐NC was administered orally at 1.5 mg/m2 per day × 5 days every week. Response evaluation was performed at 8 weeks, and those with stable or responding disease continued treatment until maximal response was achieved. A total of 56 patients (30 females and 26 males) with a median age of 55 years (range, 19–79 years) were enrolled on the study. Seventeen patients were enrolled on the GI leiomyosarcoma arm; only 1 minor response, lasting < 8 weeks in a patient with liver metastases, was noted, and so this arm was terminated. Thirty‐nine patients were entered on the other STS arm. RESULTS Three patients achieved a partial response (response rate, 8%) for durations of 4, 6, and 13 months, respectively. Fourteen patients had stable disease for a median of 4 months (range, 2–8 months). Two patients died of disease during the first 2 months. Four other patients required hospitalization for nausea, vomiting, and dehydration. Other toxicities included diarrhea (36 patients, 5 with Grade 3 toxicity); fatigue (42 patients, 11 with Grade 3 toxicity); anorexia (32 patients, 1 with Grade 3 toxicity); nausea (37 patients, 2 with Grade 3 toxicity); vomiting (24 patients, 3 with Grade 3 toxicity); neutropenia (14 patients, 5 with Grade 3 toxicity); and thrombocytopenia (16 patients, 5 with Grade 3 or 4 toxicity). CONCLUSIONS 9‐NC is well tolerated but inactive in GI leiomyosarcomas and has minimal activity in previously treated patients with STS. Cancer 2003;97:2848–52. © 2003 American Cancer Society. DOI 10.1002/cncr.11385