Gemcitabine-Containing Chemotherapy in the Treatment of Patients with Advanced Soft Tissue Sarcoma

Abstract

Background: To assess the role of gemcitabine (G) or gemcitabine-containing regimens (GCR) in advanced soft tissue sarcoma (STS), we analyzed the response rate and the time-to-progression (TTP) in advanced STS patients (pts) following G/GCR treatment. Patients and Methods: From 8/98 to 12/01, 38 pts were treated with G alone (N = 9), or GCR including docetaxel (N=14); cisplatin (N = 13); or vinorelbine or paclitaxel (N = 2). Histologies included advanced STS in 32 pts and gastrointestinal stromal tumors (GIST) in 6 pts. Thirty-three pts including 27 STS pts had been pre-treated with a median of two prior regimens. Therapy consisted of a median of 3 cycles (range: 1 - 13) of G/GCR at a median G dose/application of 909 mg/m² infused over 30 min. Results: Among the 32 non-GIST pts, there were 5 partial (15.6 %) and 2 minor (6 %) responses, with a median response duration of 17.8 + (range, 15.5 + - 63 +) weeks. In the group of 27 pre-treated STS pts, 3 partial (11 %) and 2 minor (7 %) responses were observed. With a median follow-up of 26 weeks, the median time-to-progression (TTP) was 18.4 weeks. Progression-free rates at 8, 12, and 24 weeks among pre-treated STS pts. were 73 %, 68 %, and 35 %, respectively. Conclusion: The response and PF rates observed in this analysis are comparable to those previously described for second-line anthracyclines and DTIC. Given the limited number of active cytostatic drugs for STS pts, these data suggest further evaluation of G or G-containing regimens in advanced STS.

Key words

Soft tissue sarcomas - Gemcitabine - Second-line therapy - Third-line therapy

References

• 1 Nielsen O S, Dombernowsky P, Mouridsen H. et al . High-dose epirubicin is not an alternative to standard-dose doxorubicin in the treatment of advanced soft tissue sarcomas. A study of the EORTC soft tissue and bone sarcoma group.  Br J Cancer. 1998;  78 1634-1639
• 2 Le Cesne A, Antoine E, Spielmann M. et al . High-dose ifosfamide: circumvention of resistance to standard-dose ifosfamide in advanced soft tissuesarcomas.  J Clin Oncol. 1995;  13 1600-1608
• 3 Nielsen O S, Judson I, van Hoesel Q. et al . Effect of high-dose ifosfamide in advanced soft tissue sarcomas. A multicentre phase II study of the EORTC Soft Tissue and Bone Sarcoma Group.  Eur J Cancer. 2000;  36 61-67
• 4 Buesa J M, Mouridsen H T, van Oosterom A T. et al . High-dose DTIC in advanced soft-tissue sarcomas in the adult. A phase II study of the E.O.R.T.C. Soft Tissue and Bone Sarcoma Group.  Ann Oncol. 1991;  2 307-309
• 5 Borden E C, Amato D A, Rosenbaum C. et al . Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas.  J Clin Oncol. 1987;  5 840-850
• 6 Delaloge S, Yovine A, Taamma A. et al . Ecteinascidin-743: a marine derived compound in advanced, pretreated sarcoma patients-preliminary evidence of activity.  J Clin. Onco12001;  19 1248-1255
• 7 Le C esne, Blay J Y, Judson I. et al . ET-743 is an Active Drug in Adult Soft-Tissue Sarcoma (STS): a STBSG-EORTC Phase II Trial.  Proc Am Soc Clin Oncol. 2001;  20 353a (abstr)
• 8 Merimsky O, Meller I, Flusser G. et al . Gemcitabine in soft tissue or bone sarcoma resistant to standard chemotherapy: a phase II study.  Cancer Chemother Pharmacol. 2000;  45 177-181
• 9 Spath-Schwalbe E, Genvresse I, Koschuth A, Dietzmann A, Grunewald R, Possinger K. Phase II trial of gemcitabine in patients with pretreated advanced soft tissue sarcomas.  Anticancer Drugs. 2000;  11 325-329
• 10 Okuno S H, Edmonson J H, Mahoney M R, Buckner J C, Frytak S, Galanis E. Limited activity and acceptable toxicity of gemcitabine in a phase II study of patients with advanced sarcomas: a Mayo Cancer Center study.  Proc Am Soc Clin Oncol. 2000;  19 555a(abstr)
• 11 Hensley M L, Maki R, Venkatraman E. et al . Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial.  J Clin Oncol. 2002;  20 2824-2831
• 12 Svancarova L, Blay J Y, Judson I R. et al . Gemcitabine in advanced adult soft-tissue sarcomas. A phase II study of the EORTC Soft Tissue and Bone Sarcoma Group.  Eur J Cancer. 2002;  38 556-559
• 13 Patel S R, Gandhi V, Jenkins J. et al . Phase II clinical investigation of gemcitabine in advanced soft tissue sarcomas and window evaluation of dose rate on gemcitabine triphosphate accumulation.  J Clin Oncol. 2001;  19 3483-3489
• 14 van Glabbeke M, Hogendoorn P CW, Mouridsen H. et al . Progression free rate as the principal end-point for phase II trial on soft tissue sarcoma: what should be the target? A retrospective study of the EORTC Soft Tissue and Bone Sarcoma (STBSG) database.  Proc Am Soc Clin Oncol. 2001;  20 354a(abstr)
• 15 van Glabbeke M, Verweij J, Judson I, Nielsen O S. Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas.  Eur J Cancer. 2002;  38 543-549
• 16 Verweij J, Lee S M, Ruka W. et al . Randomized phase II study of docetaxel versus doxorubicin in first- and second-line chemotherapy for locally advanced or metastatic soft tissue sarcomas in adults: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.  J Clin Oncol. 2000;  18 2081-2086
• 17 Blackledge G, van Oosterom A, Mouridsen H. et al . Doxorubicin in relapsed soft tissue sarcoma: justification of phase II evaluation of new drugs in this disease. An EORTC Soft Tissue and Bone Sarcoma Group Study.  Eur J Cancer. 1990;  26 139-141
• 18 Keohan M L, Grever M R, Balcerzak S P, Antman K. A phase II Southwest Oncology Group study of cisplatin and continuous infusion vinblastine in the treatment of advanced soft tissue sarcoma.  Invest New Drugs. 1997;  15 255-256