High‐dose cisplatin for metastatic soft tissue sarcoma

Abstract

Between August 1984 and January 1987, the Southwest Oncology Group (SWOG) registered 46 patients with metastatic sarcomas on SWOG 8465, a Phase II trial of high-dose cisplatin in patients with metastatic soft tissue sarcoma. Six patients were ineligible for the following reasons: poor performance status (two patients); ineligible diagnosis (three patients, two with Ewing's sarcoma of bone and one with metastatic chondrosarcoma); and evaluable but nonmeasurable disease (one patient with bone-only disease). Of the 40 fully evaluable patients, 34 had received prior chemotherapy; treatment was with cisplatin (40 mg/m2/d for 5 consecutive days). Cisplatin was mixed in 250 ml of 3% NaCl and hydrated with a normal saline solution at a rate of 250 ml/h, beginning 12 hours before the first dose of cisplatin was specified. The second treatment was given 3 weeks after the first, with all subsequent treatments given every 4 weeks. After three cycles of treatment, responding patients were treated at a cisplatin dose of 20 mg/m2/d for 5 consecutive days. Leukopenia was of Grade 3 or 4 in seven patients, whereas thrombopenia was of Grade 3 or 4 in eight patients. More severe myelosuppression was produced in patients who had received prior radiotherapy. A single case of reversible Grade 4 nephrotoxicity was produced; neurotoxicity was observed in 11 cases, but was of Grade 3 in only 2 cases. Of the 40 evaluable cases, six showed partial responses or no responses, for a major response rate of 15%. High-dose cisplatin has minor activity and major toxicity in the treatment of metastatic soft tissue sarcomas, and should be considered investigational.

Adriamycin and Cis-Platinum as First-Line Treatment in Unresectable Locally Advanced or Metastatic Adult Soft-Tissue Sarcomas

“…4 Platinum-derived agents including CDDP hold promise of clinical activity in the treatment of advanced STS. 9 CDDP has significant activity in pediatric and bone sarcomas, although the single-agent activity in adult STS is below 20%, basically as second-line treatment. 17 A combination of adriamycin, mitomycin-C, and CDDP induced a response rate of 43%, which was also confirmed in a large randomized study.…”

“…Numerous modifications of CDDP schedule have been attempted so far, but none has resulted in administering more than 100 mg/m 2 CDDP per cycle. 9 The list of agents with significant activity in adult STS is limited, mainly referred to ADR, dacarbazine, and ifosfamide. ADR has been the mainstay of chemotherapy for advanced STS.…”

“…8 The response rates as single agent, in phase II clinical trials, as second-line treatment in adult STS appears to be about 20%. 9 A recent randomized study using epirubicin and CDDP in patients with advanced STS showed promising results in terms of response rate, progression-free survival, and overall survival. 10 The objectives of this study were to determine the therapeutic efficacy and to evaluate the safety of the combination of ADR and CDDP as first-line treatment in advanced adult soft-tissue sarcomas.…”

High-dose chemotherapy with autologous peripheral blood stem cell transplantation for bone and soft-tissue sarcomas

“…11 Cisplatin was also included because it can have antitumor activity in sarcomas at doses of 200 mg/m 2 per course or in addition to ifosfamide. 15 The role of etoposide in the treatment of sarcoma is controversial, 31 but in vitro studies demonstrated a synergistic cytotoxic effect with cisplatin. 32 In our study, toxicity was comparable to the data of Blay et al 29 During follow-up, only three patients of the nine CR patients relapsed and two of them DOD, so that seven patients are still alive (one is AWD) and six of them are NED ( Table 1).…”

“…[10][11][12][13] Another active single agent in the therapy of STS is cisplatin with a 15% response rate using high doses (200 mg/m 2 ). 14,15 In phase-II studies different combination chemotherapy regimens based on high doses of ifosfamide, doxorubicin or cisplatin demonstrated response rates of up to 60%. 16,17 However, phase-III trials using these dose-intensive regimens demonstrated inconsistent benefits in terms of response rates and could not show an improvement in overall survival (OS).…”