Granulocyte-macrophage colony-stimulating factor alone or with dacarbazine in metastatic melanoma: a randomized phase II trial.

The potential antitumoral effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) led us to evaluate GM-CSF alone or with dacarbazine (DTIC) in metastatic melanoma in first line randomized phase II. Treatment was arm A: GM-CSF: 5 microg kg(-1), bid, 14 consecutive days every 21 days and arm B: GM-CSF: 5 microg kg(-1), bid, day 2 to day 19 every 21 days and DTIC: 800 mg m(-2), day 1 of each cycle. 32 patients (pts) were included, 15 pts in arm A and 17 in arm B. All pts had visceral metastatic sites. 9 had only one metastatic site. The median number of cycles given was 2 in arm A and 3 in arm B. 100% and 89.4% of the planned dose of GM-CSF was given in arm A and arm B respectively. No objective response was obtained. 19 pts experienced at least WHO grade 3 toxicity. All pts had fever, 29 had a decrease in performance status and 23 had pain. Grade 3 toxicity were fever (38.7%), decrease in performance status (32.3%), pain (19.4%) and dyspnoea (12.5%). In this study, GM-CSF alone or in association with DTIC did not induce any antitumoral activity with subsequent toxicity.

Prognostic factors in retroperitoneal sarcoma: a multivariate analysis of a series of 165 patients of the French Cancer Center Federation Sarcoma Group.

BACKGROUND: Surgery is the main prognostic factor in retroperitoneal sarcoma. However, despite progress, surgery alone is rarely curative, and analysis of the causes of failures and of other prognostic factors are warranted to ascertain treatment orientations. METHODS: Data of patients treated from 1.80 to 12.94 for primary retroperitoneal sarcoma were extracted from the French Federation of Cancer Centers Sarcoma Group registry. Univariate and multivariate analysis were performed for initial local control and for local and general outcome. One hundred sixty-five patients (median age, 54 years; range, 16--82 years) were identified. Median tumor size was 15 cm (range, 2--70 cm); 31% of tumors presented with neurovascular or bone involvement. Liposarcoma, leiomyosarcoma, and malignant fibrous histiocytoma represented 66% of the tumors. Eighty-four percent of the tumors were of high or intermediate grade. Twenty patients had initial metastases. Multimodality treatment included surgery (150 patients), radiotherapy (92 patients), and chemotherapy (77 patients). Complete excision was achieved in 94 of 145 nonmetastatic patients. Median follow-up was 47 months (range, 3--160 months). RESULTS: Actuarial overall 5-year survival rate (median) was 46% (51 months). The main prognostic factors for survival were initial metastases and surgery, which represented the major treatment-linked factor. High-grade of tumors affected local recurrence, metastatic recurrence, and survival. Adjuvant radiotherapy was significantly associated with reduced local recurrence. Various evolutive patterns were observed with histologic subtypes. CONCLUSIONS: Aggressive surgery remains mandatory in retroperitoneal sarcoma, but a randomized trial is needed to evaluate the place of radiotherapy for local control.

Retroperitoneal soft tissue sarcomas: a pilot study of intraoperative radiation therapy.

This pilot study was conducted to evaluate the feasibility and tolerance of a multimodal therapy of retroperitoneal soft tissue sarcoma (STS), including intraoperative radiation therapy (IORT). Nineteen patients (14 primarily treated patients and 5 treated for a recurrent tumor) were included. Surgery included a complete resection (14), a partial resection (2), and no resection (2). The median IORT dose was 17 Gy. Thirteen patients also received an external radiation therapy (ERT). Nine patients received chemotherapy. There was no postoperative mortality. Immediate postoperative complications occurred in four patients (21%). Delayed complications occurred in six patients, including one lethal iliac artery disruption. With a median follow-up of 17 months, the 2-year disease-free survival rate was 60%, and the 2-year actuarial local control rate was 76%. A multimodality approach of treatment, including IORT and ERT and eventually chemotherapy, appears feasible in patients with retroperitoneal STS. However, the treatment-related morbidity appeared relatively high in this study.

Phase II study of epirubicin in advanced soft tissue sarcoma.

Thirty-seven patients (pts) with previously untreated and measurable advanced soft tissue sarcoma entered this phase II study: 22 men and 15 women were included. Median age was 58 (range: 20-71). The starting dose of epirubicin was 100 mg/m2 IV bolus every 3 wks. In the case of minimal myelosuppression, the dose was increased by 10 mg/m2 to 130 mg/m2 (Mean dose per cycle: 105 mg/m2). Median cumulative dose of epirubicin administered was 445 mg/m2 (range: 200-1320 mg/m2). From 32 evaluable pts, one had a complete response (CR), 5 a partial response (PR), (CR + PR = 18.7% +/- 13.8%), 12 showed no change (37.5%) and 14 had progressive disease. The number of complete or partial responses observed was not modified by increasing the doses of epirubicin. Median time to progression was 4 months. From 32 pts evaluable for toxicity, hematologic toxicity at d 21 was mild. Non hematological toxicities consisted of nausea and vomiting in 74% of pts (WHO grade 3 = 5%), stomatitis in 12.2% (WHO grade 3 = 3%) and alopecia in 91% (WHO grade 2-3 = 72%). No cardiac dysfunction was recorded during the treatment, even though 7 patients received more than 800 mg/m2 of epirubicin (median: 850 mg/m2, range: 810-1320 mg/m2). The results of this study show that epirubicin is an active drug in advanced soft tissue sarcoma.