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

Abstract

BACKGROUNDThe 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).METHODSPatients 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.RESULTSThree 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).CONCLUSIONS9‐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

Developing therapeutic pharmaceuticals for the treatment of soft-tissue sarcomas

“…Three patients (with malignant fibrous histiocytoma [MFH], extraskeletal Ewing's and extraskeletal chondrosarcoma), out of a total of 39, achieved a PR for a response rate of 9%. Toxicities included diarrhoea, fatigue, anorexia, nausea, vomiting and myelosuppression, which were manageable [21]. In another study of 9-NC at a dose of 1.25 mg/m 2 o.d.…”

Current Role of Topoisomerase I Inhibitors for the Treatment of Mesenchymal Malignancies and Their Potential Future Use as Payload of Sarcoma-Specific Antibody-Drug Conjugates

“…Phase 1 Studies in Patients with Solid Tumors Rubitecan has been evaluated in numerous phase 1 studies, with different formulations, in solid tumors and leukemia [18]. In a study in solid tumors, in patients treated with 1, 1.5, or 2 mg/m 2 /day for 5 days followed by 2 days of rest, the DLT was hematologic, gastrointestinal AEs were the next most significant AEs, and the RP2D was 1.5 mg/m 2 /day for 5 days each week [52].…”

Potential Combination Chemotherapy Approaches for Advanced Adult-Type Soft-Tissue Sarcoma

“…Given the encouraging response rates mentioned above and the tive of the plant alkaloid camptothecin, was shown to be effective fact that remissions are comparably durable, [49,54] trabectedin is an in STS, inducing partial responses in 3 of 39 patients with different attractive substance with potential activity in combination chemo-STS histologies (response rate 8% [CI 95% 0, 16]). [71] Topotecan, therapy regimens. Brostallicin is also currently being investigated another DNA topoisomerase I inhibitor, has been evaluated and versus doxorubicin in a randomized EORTC STBSG phase II trial found to be ineffective in pretreated STS.…”