Performance status is the most powerful risk factor for early death among patients with advanced soft tissue sarcoma: the European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (STBSG) and French Sarcoma Group (FSG) study.

BACKGROUND: We investigated prognostic factors (PFs) for 90-day mortality in a large cohort of advanced/metastatic soft tissue sarcoma (STS) patients treated with first-line chemotherapy. METHODS: The PFs were identified by both logistic regression analysis and probability tree analysis in patients captured in the Soft Tissue and Bone Sarcoma Group (STBSG) database (3002 patients). Scores derived from the logistic regression analysis and algorithms derived from probability tree analysis were subsequently validated in an independent study cohort from the French Sarcoma Group (FSG) database (404 patients). RESULTS: The 90-day mortality rate was 8.6 and 4.5% in both cohorts. The logistic regression analysis retained performance status (PS; odds ratio (OR)=3.83 if PS=1, OR=12.00 if PS ≥2), presence of liver metastasis (OR=2.37) and rare site metastasis (OR=2.00) as PFs for early death. The CHAID analysis retained PS as a major discriminator followed by histological grade (only for patients with PS ≥2). In both models, PS was the most powerful PF for 90-day mortality. CONCLUSION: Performance status has to be taken into account in the design of further clinical trials and is one of the most important parameters to guide patient management. For those patients with poor PS, expected benefits from therapy should be weighed up carefully against the anticipated toxicities.

Doxorubicin and cisplatin chemotherapy in high-grade spindle cell sarcomas of the bone, other than osteosarcoma or malignant fibrous histiocytoma: a European Osteosarcoma Intergroup Study.

There are limited data that define the role of chemotherapy in the treatment of high-grade spindle cell sarcomas of bone, other than osteosarcoma or malignant fibrous histiocytoma (MFH-B). This prospective study evaluates the effect of doxorubicin and cisplatin on these tumours. Thirty-seven patients, age 65 years, with spindle cell sarcoma of bone, except osteosarcoma or MFH-B, were included. Chemotherapy consisted of doxorubicin and cisplatin every 3 weeks for six cycles. Resection was performed after three cycles. In 15 patients with metastases, response assessment showed three complete responses (CR), four stable disease (SD), five progression; three were not evaluable. Median time to progression was 30 months (95% Confidence Interval (CI), 8-51 months) for the operable non-metastatic patients; median survival 41 months (95% CI, 16-82 months). Median time to progression in the metastatic group was 10 months (95% CI, 0-18 months) and median survival was 14 months (95% CI, 4-45 months). This study suggests a limited role for doxorubicin and cisplatin in metastatic high-grade spindle cell sarcoma of bone, other than osteosarcoma or MFH-B cases.

Palliative therapy of melanoma patients with fotemustine. Inverse relationship between tumour load and treatment effectiveness. A multicentre phase II trial of the EORTC-Melanoma Cooperative Group (MCG).

Fotemustine (FM) is a new chloronitrosurea (CNU), chemically characterized by the graft of an aminophosphonic acid on the CNU radical, which makes it highly lipophilic. Following single-institution phase I and II studies with remarkably high response rates of some 40%, including brain metastases of 25% and more, the EORTC-MCG started a multicentre phase II trial to confirm these results according to EORTC guidelines. Treatment consisted of an induction cycle of FM (100 mg/m2 on days 1 + 8 + 15), followed by maintenance courses (q3w). Fifty-four patients were entered by 11 institutions. General interest in this promising new agent, however, led clinicians of six additional institutions to join the EORTC trial and 90 more patients were included in only 4 months. This rapidly rising accrual rate became inversely related to the physicians' adherence to the eligibility criteria: palliation of symptoms rather than clinical research was the dominant reason to start treatment. Clinical characteristics and results in the eligible vs non-eligible patient group (in parentheses) were as follows: male/female 29/26 (68/65), mean age 54 years (53), ECOG-PS 0-1 (0-4), CR 2 (0), PR 10 (2), NC 17 (5) and for brain metastases: PR 4 (1), NC 2 (1), for an ORR of 12% (5%). Median duration of response was 6 months (range 4-16). The clinically relevant toxicity was limited to the haematopoiesis with delayed platelet nadirs (30% grade III+IV), granulocyte (25% grade III + IV) and the gastrointestinal tract: nausea and vomiting (26% grade II, 18% III, 1% IV). This study confirms that FM is active in melanoma including brain metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-dose total body irradiation versus combination chemotherapy for lymphomas with follicular growth pattern.

The treatment of Non-Hodgkin's lymphomas with follicular growth pattern and advanced stage of disease remains controversial. Treatments varying from no initial treatment up to aggressive combination chemotherapy have been advocated. The EORTC Lymphoma Cooperative Group has performed a randomized prospective trial comparing short duration low dose total body irradiation (TBI) vs combination chemotherapy (CHVmP) + consolidation radiotherapy. Ninety-three patients were entered; of 84 evaluable patients, 44 received TBI and 40 CHVmP. Complete remission (CR) rates were 36%--TBI and 55%--CHVmP, but overall response rates were identical, 76 versus 69%. No significant difference in freedom from progression or survival was observed. No unexpected toxicity was seen. Although numbers are small, we cannot conclude that aggressive combination chemo-radiotherapy resulted in a better survival. Our analysis confirms that there is a constant risk of relapse. Other approaches should be explored if survival benefit is the ultimate goal in treatment of this patient population.