Doxorubicin (Adriamycin) was administered by continuous infusion to reduce peak plasma levels and thus lessen cardiac toxicity. Cardiotoxicity was monitored by noninvasive methods, and endomyocardial biopsy specimens were studied by electronmicroscopy. Cardiotoxicity was compared in 21 patients receiving doxorubicin intravenously over 48 or 96 hours and in 30 control patients treated by standard intravenous injection. Both groups were studied prospectively and were well matched by risk factors for doxorubicin cardiotoxicity. The median cumulative dose for those receiving continuous infusion was 600 mg/m2 body surface area (range, 360 to 1500 mg/m2) compared with 465 mg/m2 (range 290 to 680 mg/m2) in the control group (p = 0.002). Fourteen of the 30 patients in the control group showed severe morphologic changes in the biopsy specimens, precluding further doxorubicin administration, as compared with two of 21 patients receiving the drug by continuous infusion (p less than 0.02). The mean pathologic score for the infusion group, 0.9, was lower than the mean for the control group, 1.6 (p = 0.004). Antitumor activity was not compromised. Decreasing peak plasma levels of doxorubicin by continuous infusion reduces cardiotoxicity.

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.

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.

The sequential combination of CVD with IL-2 + IFN-alpha appears to have produced an increase in the number of durable responses in patients with metastatic melanoma. The toxicity of this program, although severe, was manageable. The biochemotherapy regimen produced an apparent increase in the median survival compared to that observed with the CVD regimen. However, a prospective comparison of these two regimens will be required to confirm these observations.

Based on the independent activity of cisplatin, vinblastine, and dimethyl-triazeno-imidazole-carboxamide (DTIC) (CVD), a combination of these agents was used in the treatment of patients with advanced mel-anoma. Vinblastine was used in a dose of 1.6 mg/m2/d for 5 days, DTIC was used in a dose of 800 mg/ m2 intravenously (IV) on day I, and cisplatin was used in a dose of 20 mg/m2/d for 4 days starting on day 2 of chemotherapy. The courses of chemotherapy were repeated at 3-week intervals. All patients were premedicated with antiemetics, and IV hydration was used before cisplatin. Fifty-two consecutive patients were registered and 50 were evaluable for response. Two patients achieved a complete response (CR) and 18 patients had a partial response (PR) for an overall response rate of 40% (95% confidence interval, 27% to 55%). The median duration of response was 9 months and the median survival time of the responders was 12 months. The overall median survival time of patients treated on this protocol was 9 months. The treatment was associated with significant toxicity consisting of nausea, vomiting, diarrhea, and partial hair loss. Additionally, neutropenia with a median nadir granulocyte count of 500/~1 was observed, and significant anemia required blood transfusions in a majority of the patients after three to four courses of chemotherapy. The dose-limiting toxicity was peripheral neuropathy which required dis-continuation of cisplatin after six to eight courses of chemotherapy. We believe that this triple-drug regimen has significant activity that appears to be superior to the single-agent activity of these drugs, both in terms of increased response rate and duration of response.

The purpose of this study was to review the clinical course of patients diagnosed with vulvar melanoma. Charts of patients diagnosed between 1970 and 1997 were reviewed for demographics, lesion characteristics, disease duration and extent, and treatments. Actuarial survival curves were computed by the Kaplan Meier method and compared by Cox proportional hazards regressions. Fifty-one patients (median age 54) with vulvar melanoma presented with a vulvar mass (39%), pain (30%), bleeding (24%), and itching (20%). Anatomical distribution was mucosa of the vulva (65%), vulvar epidermal site (21%), or unspecified vulva (14%), with 20% having multifocal disease at diagnosis. Histologic types were superficial spreading or nodular (50% each). Median lesion characteristics were diameter 2 cm, Breslow index 4.4 mm, and Clark level IV. Distribution of patients per American Joint Committee on Cancer (AJCC) stage was 29%, 50%, 16%, and 7% for stages I, II, III and IV, respectively. Inguinal node metastases were unilateral in 16% and bilateral in 7%. Despite complete surgical resection, 32 patients (63%) recurred. Median survival for all patients was 41 months (range, 5-324), with 91% 5-year survival for patients with stage I and 31% for stage >or= IIA (P = 0.0002). As with cutaneous melanoma, the AJCC classification, Breslow's thickness, and Clark's levels are the major predictors of overall survival (P = 0.0001 each) and disease-free survival (P