Our analysis showed that the current AJCC staging system has many inaccuracies that should be modified to conform to published data. On the basis of our analysis and review of the literature, we propose a new and more accurate staging system.

Cytokines substantially augment the antitumor activity of chemotherapy at the expense of considerable toxicity in patients with metastatic melanoma.

Background. Liver metastasis develops in approximately two‐thirds of patients with recurrent uveal melanoma. Despite therapy, the median survival of those with liver metastasis is 5 to 7 months. The recognition of a grave prognosis associated with liver metastasis has led to evaluation of new modalities of therapy, including the use of regional therapies such as intrahepatic arterial chemotherapy and either embolization or chemoembolization of hepatic metastases. In this study, the results of an institutional experience over the past 2 decades are reviewed and prognostic factors that affect survival from the time the liver metastasis is diagnosed are assessed. Methods. In this study of 201 patients with uveal melanoma involving the liver who were treated at M. D. Anderson Cancer Center between 1968 and 1991, the authors retrospectively reviewed the cases and compared the results of systemic therapies, hepatic infra‐arterial chemotherapies, and chemoembolization of liver metastases. Cox's multivariate analysis and stepwise logistic regression were then computed to determine significant prognostic variables. Results. The systemic therapies produced a response rate of less than 1%. Chemoembolization was the most effective treatment, inducing responses in 36% of patients. Survival curves were calculated using the life‐table method of Kaplan and Meier. Patient‐and tumor‐related characteristics were examined and their relation to on survival from the time of diagnosis of liver metastasis was determined. Levels of serum alkaline phosphatase, total bilirubin, and lactic dehydrogenase plus response to treatment showed a strong relation to survival. In contrast, univariate analysis showed that patient age and gender, metastasis free interval, presence of extrahepatic metastasis, and type of therapy for liver metastasis did not influence survival. Multivariate stepwise regression analysis identified serum alkaline phosphatase and metastasis free interval as the main independent prognostic factors for survival after liver metastasis diagnosis. Conclusions. Of the three modalities of therapy used for choroidal melanoma metastatic to the liver, only chemoembolization using cisplatin‐based regimens produced a meaningful response rate. Information from this analysis can be used to predict the outcome of patients with uveal melanoma metastatic to the liver. Patients with metastatic ocular melanoma confined to the liver should be treated with chemoembolization and should not be included in chemotherapy trials designed for cutaneous melanoma. Cancer 1995; 76:1665–70.

Concurrent biochemotherapy for patients with advanced melanoma is capable of producing high CR and overall response rates and resulted in durable complete remissions in a small fraction of patients. Toxicity, although severe, was manageable in a routine inpatient hospital environment.

Given the limited therapeutic armamentarium for STS, the activity of gemcitabine is encouraging. Its potential for combination therapy in the salvage setting should be studied with pharmacologically guided fixed dose-rate infusion.

This study supports the use of stratification parameters that reflect the favorable prognostic impact of soft tissue or single visceral organ metastases and normal serum levels of LDH and albumin at time of enrollment in advanced melanoma trials. Improved survival over the prior decade probably reflects advances in diagnostic and palliative interventions.

HDI at 14 g/m2 with mesna and G-CSF is an active salvage regimen for patients with bone and soft tissue sarcomas. There is a definite positive dose-response curve, and bolus administration appears to be more active than continuous infusion.

The authors evaluate the efficacy and feasibility of dose-intensive doxorubicin and ifosfamide combination chemotherapy in patients with sarcomas. From January 1995 to April 1996, 33 evaluable patients with either metastatic sarcoma or primary sarcomas with a high-risk for metastases (all except one was previously untreated with chemotherapy) were treated on two consecutive protocols. The median age was 45 years (range, 15-68 years). The first protocol included doxorubicin at 75 mg/m2 given as a 72-hour infusion on days 1 to 3 along with ifosfamide at 2 g/m2/d over 2 hours x 5, days 1 to 5 (protocol AI 75/10). Granulocyte colony-stimulating factor (G-CSF) was used only if indicated according to American Society of Clinical Oncology guidelines. The second protocol included doxorubicin at 90 mg/m2 as a 72-hour continuous infusion and ifosfamide at 2.5 g/m2/d for 4 days (protocol AI 90/10) with prophylactic G-CSF. A median of four cycles were administered (range, 1-6). Three patients achieved a pathologic complete response (CR) and 18 patients achieved a partial response (PR) for a response rate (RR) of 64% (95% confidence interval (CI), 45-80%). Response rate for the subset of patients with soft-tissue sarcomas was 66% (95% CI, 46-82%). Only three patients progressed on therapy. Febrile neutropenia was noted in 31% of cycles at AI 75/10 and in 56% of cycles at AI 90/10. One patient developed reversible grade 3 central nervous system (CNS) toxicity. There was one treatment-related death on AI 90/10 secondary to doxorubicin cardiac toxicity at a cumulative dose of 435 mg/m2. Dose-intensive doxorubicin plus ifosfamide is feasible in appropriately selected patients and appears to be a very active regimen in patients with sarcomas. The authors are currently testing this regimen with G-CSF and thrombopoietin.