Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: A Gynecologic Oncology Group phase II study

Abstract

Objective-Doxorubicin-based treatment is standard therapy for metastatic uterine leiomyosarcoma. There is no standard second-line therapy. We determined activity of fixed-dose rate gemcitabine plus docetaxel as second-line treatment for metastatic uterine leiomyosarcoma.Methods-Eligible women with unresectable uterine leiomyosarcoma progressing after prior cytotoxic therapy were treated with gemcitabine 900 mg/m 2 days one and eight over 90 minutes, plus docetaxel 100 mg/m 2 on day 8 of a 21-day cycle with granulocyte growth factor. Patients with prior pelvic radiation received lower doses. Response Evaluation Criteria in Solid Tumors (RECIST) response was assessed by computed tomography (CT).Results-Forty-eight of 51 women were evaluable for response (one wrong histology, two never treated). Prior therapy was doxorubicin-based in 90%, and ifosfamide-based in 6%. The overall objective response rate is 27%, with complete response in 6.3% (3/48), and partial response in 20.8% (10/48). An additional 50% (24/48) had stable disease (median duration 5.4 months). The median number of cycles per patient was 5.5 (range 1-22); 73% of patients remained progression-free at 12 weeks and 52% at 24 weeks. The predominant toxicity was uncomplicated myelosuppression: thrombocytopenia grade 3 (29%), grade 4 (10.4%); neutropenia grade 3 (12.5%), grade 4 (8.3%) anemia grade 3 (20.8%), grade 4 (4.2%). While pulmonary toxicity was reported, no patient had drug-related pneumonitis/hypoxia-type toxicity. Median progression-free survival (PFS) was 5. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript months (range 0.7 -27+ months). The median duration of objective response was 9+ months (range 3.9 -24.5+ months).Conclusion-Fixed-dose rate gemcitabine plus docetaxel is active second-line therapy for uterine leiomyosarcoma.

Randomized Multicenter and Stratified Phase II Study of Gemcitabine Alone Versus Gemcitabine and Docetaxel in Patients with Metastatic or Relapsed Leiomyosarcomas: A Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) French Sarcoma Group Study (TAXOGEM study)

“…A fixed-dose-rate infusion of gemcitabine at 10 mg/m 2 per minute may offer a pharmacologic advantage and has also been explored [25,28,29]. The activity of single-agent docetaxel has been reported to be quite limited, with response rates of 0%-18% [30 -32].…”

A retrospective study on combination therapy with ifosfamide, adriamycin and cisplatin for progressive or recurrent uterine sarcoma

“…The overall response rate and disease control rate were 20.0 and 60.0%, respectively. Hensley et al (16,17) investigated docetaxel (DOC) + GEM therapy in 42 patients with uterine LMS. The adverse events were grade ≥3 neutropenia in 17.0%, grade ≥3 anemia in 24.0% and grade ≥ thrombocytopenia in 14.5% of the cases.…”

Efficacy and Toxicity of Gemcitabine Plus Docetaxel Combination as a Second Line Therapy for Patients with Advanced Stage Soft Tissue Sarcoma

“…In addition, the objective response rate and median overall survival were also reported as 53 % and 17.9 months, respectively. In a another phase II study reported by Hensley et al (2008) the fixed-dose rate gemcitabine plus docetaxel was evaluated only as a second line therapy in patients with metastatic uterine leiomyosarcoma. In that study, the objective response rate and median OS were demonstrated as 27% (6.3% CR) and 14.7 months, respectively.…”