Estrogen plus progestin increase superoxide dismutase and total antioxidant capacity in postmenopausal women.

OBJECTIVE: This cross-sectional study aimed to evaluate the behavior of blood antioxidant enzymes (superoxide dismutase (SOD), catalase and glutathione peroxidase), plasma total antioxidant capacity and oxidative damage (lipid oxidation and protein carbonyl levels) and their relationship with the serum levels of steroid hormones in premenopausal and postmenopausal women without and with estrogen alone (ET) or estrogen plus progestin therapy (EPT). METHODS: Blood was collected from four groups of subjects: premenopausal women (n = 24), postmenopausal women without hormone therapy (n = 31), postmenopausal women with ET (n = 12) and postmenopausal women with EPT (n = 16). RESULTS: The activities of the different SOD isoforms (CuZnSOD and MnSOD) and the plasma total antioxidant power were significantly higher in the postmenopausal women under EPT than in the postmenopausal women without hormone replacement therapy (HRT). Only CuZnSOD activity was increased in women receiving ET compared to the postmenopausal women without HRT. However, no differences were observed in the levels of lipid or protein oxidation or in the non-enzymatic plasma antioxidants (uric acid and albumin) among the groups. The duration of HRT and serum estrogen levels were positively correlated to the blood CuZnSOD activity and to plasma total antioxidant power, whereas the serum progesterone levels were positively correlated to CuZnSOD activity and negatively correlated to protein carbonyl groups. Interestingly, the total antioxidant power of plasma was positively correlated to CuZnSOD and glutathione peroxidase activities. CONCLUSION: We conclude that EPT increases blood MnSOD and CuZnSOD activity in postmenopausal women, leading to an increased plasma total antioxidant capacity. This finding may be relevant to the prevention of oxidative stress-related disorders in postmenopausal women.

Cytogenetic diagnosis of cancer: abnormalities of chromosomes and polyploid levels in the bone marrow of patients with small cell anaplastic carcinoma of the lung.

The chromosomes of metastatic cells and polyploid levels in the bone marrow of 26 patients with small cell anaplastic carcinoma were studied by direct bone marrow preparation and trypsin-Giemsa banding. Eighteen of these patients had received no tumor therapy and 8 had had chemotherapy and/or radiation therapy; 18 patients, including 5 who had received therapy, had karyotypic abnormalities with or without elevation of the polyploid level. Modal numbers and chromosome abnormalities were highly variable in treated and untreated patients. Modes ranged from hypodiploid to polyploid, but polyploid modes were the most frequently observed abnormal modes. Polyploid modes were not seen, however, in post-therapy patients with the exception of one who had received radiation therapy to the mediastinum for only 4 days prior to withdrawal of the specimen for chromosome analysis. Ten patients had elevated polyploid levels that ranged from 4.24 to 44.8% and always occurred in conjunction with karyotypic abnormalities. Both aneusomy (abnormal number) of normal chromosomes and structural aberrations (markers) occurred frequently. Some markers were consistent within an individual, but other variable aberrations were also typically present. Very few markers were common to 2 or more patients. The no. 1 chromosome participated in marker formation in 14 of the 18 patients with karyotypic abnormalities. Of the 26 patients, 5 were negative for metastasis to the marrow by pathologic examination but positive by cytogenetic diagnosis, whereas none were positive by pathologic examination and negative by cytogenetic diagnosis; this demonstrated that cytogenetics may be used as a rapid adjunct diagnostic procedure for the detection of metastasis in the marrow.

Isolation and characterization of a hormone-producing cell line from human small cell anaplastic carcinoma of the lung.

A continuous cell culture line was established from a bone marrow metastasis of small cell anaplastic carcinoma of the lung. The cultures were characterized by light and electron microscopy, and an unusual concentric arrangement of cells was observed, both in sectioned material from the patient's tumor and from the cell cultures. The cells had two types of specialized cell junctions and contained secretory-like granules of the type described in neuroendocrine cells. Lactic dehydrogenase isozyme patterns were the same as those observed in normal human serum, and the karyotype revealed the presence of several marker chromosomes. Vasopressin was present in the cells and secreted into the culture medium in the absence of neurophysin, as shown by the immunoperoxidase technique and radioimmunoassay. Oxytocin was also absent from cells.

Calcitonin as an indicator of the response of human small cell carcinoma of the lung cells to drugs and radiation.

A calcitonin (CT)-producing cell line (DMS53) established from human small cell carcinoma of the lung was grown as three-dimensional multicellular spheroids in spinner culture or on agar in multiwells, and as tumors in nude (athymic) mice. CT release into the media was directly proportional to spheroid volume. The response of these cells following exposures to X-irradiation, Adriamycin, or diazoacetylcholine iodide was assessed by monitoring levels of CT released into the media by individual spheroids. Levels of CT in the blood of nude mice bearing DMS53 xenografts were directly proportional to tumor volume and decreased proportionally with tumor response to X-irradiation and cisplatin treatment. These results suggest that the DMS53 spheroid and xenograft models may be useful systems to monitor responses to therapy utilizing CT as an indicator of tumor burden.

Outcomes and complications of continuous intraspinal narcotic analgesia for cancer pain control.

Preliminary reports of continuous intraspinal morphine analgesia have been enthusiastic regarding the resultant cancer pain control. Reports of continuous intraspinal infusion have not documented the duration of useful analgesia, need for concomitant analgesic therapies, or complication rates. Thus, the overall outcomes and complications of six chronic intrathecal and eight epidural morphine infusions were analyzed in the first 14 cancer pain patients implanted with continuous intraspinal morphine infusion reservoirs at this clinic. A five-point scale was used to assess the analgesic therapy required to maintain pain control during three consecutive intervals of intraspinal morphine infusion (zero to two months, two to six months, after six months). Comparison with pre-implant narcotic requirements revealed equal or reduced narcotic use for up to six months of therapy, with a definite trend toward escalation of intraspinal narcotics, systemic analgesia, and adjunctive procedures after two months. This occurred most likely due to narcotic tolerance and disease progression. Failure of pain control was the rule with continuous intraspinal morphine after six months. Three patients ultimately required neurolytic blocks. No clear difference was found in pain control requirements between epidural and intrathecal morphine infusion. No infection or respiratory depression occurred as a direct result of the intraspinal morphine implanted system.

Combined modality therapy with radiotherapy, chemotherapy, and immunotherapy in limited small-cell carcinoma of the lung: a Phase III cancer and Leukemia Group B Study.

Patients with limited-stage small-cell carcinoma of the lung (SCCL) were randomly assigned to a four-drug chemotherapy program consisting of methotrexate, doxorubicin, cyclophosphamide, and CCNU (MACC) or to a regimen consisting of cyclophosphamide, CCNU, and vincristine alternated with Adriamycin (Adria Laboratories, Columbus, Ohio) and vincristine (CCV/AV). All patients received 4,500 cGy, in a split course, to the primary tumor, mediastinum, and supraclavicular lymph node drainage areas and 3,000 cGy to the whole brain. After four cycles of chemotherapy, patients were randomly assigned to chemotherapy plus methanol extractable residue of BCG (MER-BCG) or no MER-BCG. The complete response frequencies were similar for the two regimens (54% and 48%) as were the median survivals (12.0 and 11.5 months) and the two-year survival rates (15% and 17%). Immunotherapy with MER-BCG did not prolong the time to disease progression or improve survival. Women had a greater chance of achieving a complete remission independent of performance status. There was a complex interaction between sex and the chemotherapy regimens that may have important implications for the design and stratification of future trials in SCCL.

Intensive combination chemotherapy, concurrent chest irradiation, and warfarin for the treatment of limited-disease small-cell lung cancer: a Cancer and Leukemia Group B pilot study.

PURPOSE: In prior Cancer and Leukemia Group B (CALGB) studies, combined chemotherapy and thoracic irradiation was superior to chemotherapy alone in limited-disease (LD) small-cell lung cancer (SCLC). A combined modality pilot study was performed to test the feasibility of adding warfarin to aggressive chemoradiotherapy for LD SCLC. PATIENTS AND METHODS: Combination chemotherapy with doxorubicin 45 mg/m2 intravenously (IV) on day 1, cyclophosphamide 800 mg/m2 IV on day 1, and etoposide (ACE) 80 mg/m2 on days 1 to 3 was given every 21 days for the first three courses. The fourth and fifth courses substituted cisplatin 33 mg/m2 IV on days 1 to 3 for the doxorubicin, with concurrent chest irradiation to a total of 4,000 cGy given in 20 fractions during a 4-week period followed by a boost of 1,000 cGy in five fractions during a 1-week period. Prophylactic cranial irradiation, 3,000 cGy was given concurrently in 10 fractions during a 2-week period. Courses 6 to 8 again used ACE chemotherapy, but courses 4 to 8 were given on a 28-day schedule with dose adjustment for hematologic or renal toxicity. Warfarin was given throughout the treatment period titrated to achieve a prothrombin time (PT) of 1.5 to 2 times the control. Patients with histologically proven limited-stage SCLC, good performance status, and normal renal, hematologic, and hepatic functions were eligible. RESULTS: Sixty-one of 66 patients entered onto the study were eligible and assessable. Fifty-four (89%) (95%) confidence interval [CI], 78% to 95%) experienced an objective response, 35 (57%) achieved a complete response (CR) (95% CI, 44% to 70%), and 17 (28%) achieved a partial response (95% CI, 16% to 39%). Median durations were CR, 26.3 months; failure-free survival, 11.8 months; and survival, 18 months. Forty-one percent of the patients were alive at 2 years, 33% were alive at 3 years, and 25% were alive at 4 or more years. Median follow-up for survivors is 5 years (range, 3.5 to 5.9 years). Severe or life-threatening myelosuppression occurred in 90%, infection occurred in 34%, fever without documented infection occurred in 26%, and pulmonary toxicity occurred in 6%. Another 6% of patients experienced severe or life-threatening hemorrhages. There were four treatment-related fatalities. The pulmonary toxicities have been associated with the resumption of ACE chemotherapy after chest irradiation. CONCLUSIONS: These highly encouraging response and survival results compare favorably with any prior CALGB group study. Although they are somewhat more toxic, they are comparable to the best published results. A randomized study that examines the role of warfarin is underway.

Prognostic factors in small-cell carcinoma of the lung: an analysis of 1,521 patients.

Cancer and Leukemia Group B (CALGB) accrued 1,745 patients with limited (LD) or extensive (ED) small-cell lung cancer (SCCL) to five separate trials between 1972 and 1986. We reviewed these data to evaluate the impact of pretreatment prognostic factors on outcome. In multivariate analysis, female gender was predictive of improved response (LD, P = .01; ED, P = .04) and survival (LD, P = .01; ED, P = .02). A performance status of 0 or 1 was associated with improved response rates in both subsets, but was statistically significant (P = .04) only for overall objective response in LD patients. Performance status was a highly significant predictor of survival in both LD and ED groups (P less than .001). Supraclavicular lymph node involvement, while still LD, had a borderline unfavorable impact on survival (P = .06) compared with a lesser extent of LD involvement. In ED patients, a decrease in survival rates was associated with an increased number of metastatic sites (P = .01). Changes in the patient population were noted with time: the percentage of women increased from 21% to greater than 35%; an increased number of metastatic sites was identified among ED patients; mean performance status improved for both LD and ED subsets. These trends reflect the changing demographics of lung cancer, improved lung cancer staging, and probably lead-time bias. Response rates, overall survival, and long-term (greater than 2-year) survival varied significantly among the five protocols, both before and after multivariate correction for identified prognostic variables. However, the changing character of the study population limits the ability to determine retrospectively how much improvements in therapy contributed to the positive changes in failure-free survival, overall survival, and long-term survival observed in our sequentially studied population.

Socioeconomic status and cancer survival.

Survival data from eight Cancer and Leukemia Group B (CALGB) protocols were examined for patients with lung cancer (N = 961), multiple myeloma (N = 577), gastric cancer (N = 231), pancreatic cancer (N = 174), breast cancer (N = 87), and Hodgkin's disease (N = 58). After accounting for differences in survival rate attributable to type of cancer, initial performance status, age, and 14 other protocol-specific prognostic indicators, the additional predictive value of socioeconomic status (SES) was evaluated. Race (white v non-white) was not a significant predictor of survival time, but income and education were. People with lower annual incomes (below $5,000 per year in the years 1977 to 1981) and those with lower educational level (grade school only) showed survival times significantly shorter than those with higher income or education, respectively. These survival differences were associated with, but could not be fully explained by, severity of disease at initial presentation. SES continued to exert a small but significant impact on cancer survival, even after controlling for all known prognostic variables. Economically and educationally disadvantaged cancer patients may require treatment programs that include education about treatment and compliance, even after an initial diagnosis is made and treatment is initiated. Because SES is related to survival independent of all known prognostic variables, it should be included in the data bases of clinical trial groups to provide a more accurate test of the effectiveness of new therapies.

Randomized trial of chemotherapy and radiation therapy with or without warfarin for limited-stage small-cell lung cancer: a Cancer and Leukemia Group B study.

PURPOSE: Studies by the Veterans Administration Cooperative Studies Program and Cancer and Leukemia Group B (CALGB) suggested that the addition of warfarin to chemotherapy might enhance response and/or survival in small-cell lung cancer (SCLC). This randomized study evaluated the effect of warfarin with chemotherapy and radiation therapy in limited-stage SCLC. PATIENTS AND METHODS: Patients were randomized to receive warfarin or no warfarin. All patients received three cycles of doxorubicin, cyclophosphamide, and etoposide (ACE). Cycles 4 and 5 (cisplatin, cyclophosphamide, and etoposide [PCE]) were given concurrently with radiation therapy. Three cycles of ACE were given after chemoradiation therapy, but were discontinued due to a high rate of pulmonary toxicity. RESULTS: There were no significant differences in response rates, survival, failure-free survival, disease-free survival, or patterns of relapse between the warfarin-treated and control groups. In patients treated according to the initial design, an increase in failure-free survival seen with warfarin treatment approached significance (P = .07). Preamendment results, while not significant, did not have superimposable treatment survival curves. A landmark analysis at 8 months showed a median survival time after the landmark for complete responders of 33 months with warfarin treatment compared with < or = 13.75 months for complete or partial responders not treated with warfarin (P = .05). Differences between the complete responders in this preamendment population were not significant (P = .103). CONCLUSION: Warfarin does not appear to improve outcome significantly in limited-stage SCLC. However, the differences in some variables between populations before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies.

Psychologic and neuropsychologic functioning of patients with limited small-cell lung cancer treated with chemotherapy and radiation therapy with or without warfarin: a study by the Cancer and Leukemia Group B.

PURPOSE: The current study assessed the psychologic and neuropsychologic functioning of patients with small-cell lung cancer who were randomized in a large clinical trial to receive intensive doxorubicin, cyclophosphamide, etoposide (ACE)/cisplatin, cyclophosphamide, etoposide (PCE) chemotherapy and radiation therapy (RT) to the primary tumor and prophylactic whole-brain irradiation with (regimen I) or without (regimen II) warfarin. PATIENTS AND METHODS: Patients' emotional states and cognitive functioning were assessed using the Profile of Mood States (POMS) and Trail Making B Test (Trails B), respectively. Two hundred ninety-five patients completed the POMS and Trails B at pretreatment, 224 patients after the completion of the ACE course of chemotherapy (week 9), and 177 patients after the completion of the PCE chemotherapy and RT (week 17). RESULTS: No differences on the POMS or Trails B measures were found between the two treatment arms as predicted, given that the only difference between the two treatment arms was the presence or absence of warfarin. Analysis of the POMS revealed that, overall, mean scores remained stable over the course of treatment; however, women showed a trend toward higher mean scores, which indicated a higher level of distress, compared with men at the pretreatment assessment. Examination of cognitive functioning, measured by the Trails B, revealed improved performance from baseline to post-ACE chemotherapy, which is consistent with a practice effect, but a significant worsening of Trails B scores post-RT compared with the pre-RT assessments, which is consistent with impaired cognitive functioning because of treatment (P < .0001). CONCLUSION: Emotional state, measured by the POMS, did not differ between the groups or change significantly over time in this study of small-cell lung cancer patients treated with a combination of chemotherapy and RT plus or minus warfarin. However, the pattern of relatively stable POMS scores and poorer Trails B performance post-RT suggested that this combination of chemotherapy and RT had a negative impact on cognitive functioning.

Human neurophysins as potential tumor markers for small cell carcinoma of the lung: application of specific radioimmunoassays.

A study of 61 patients with small cell carcinoma of the lung using specific RIAs for 2 human neurophysins (HNPs) has revealed that plasma levels of 1 or both HNPs are substantially elevated (> 3 times) in 62% of the patients before the commencement of therapy. These elevated HNPs may be a consequence of production/release by tumor. Eighteen patients with elevated plasma HNPs and 14 with normal values were followed during therapy. All of the patients with normal pre-therapy levels maintained these normal levels regardless of the course of their disease. For all patients with elevated HNP levels before therapy, there was good agreement between changes in these elevated values and clinically assessed responses. Partial or complete remission (12 patients) was associated with a 2- to 30-fold reduction in HNP levels, progressive disease (6 patients) was associated with a rise in HNP levels, and relapse after a previous objective response (6 patients) was associated with an increase in plasma HNPs over values found during remission. For many of the patients in clinical remission, HNPs remained elevated above normal values, and RIA data seem to forecast recurrent disease several weeks before clinical recognition. These data provide good evidence that our RIAs for HNPs can provide a valuable guide to therapeutic management of small cell carcinoma of the lung.

Psychosocial aspects of neoplastic disease: I. Functional status of breast cancer patients during different treatment regimens.

The authors studied 146 breast cancer patients representing three different treatment regimens by means of a structured interview, open-ended questions, and a modified Psychiatric Status Schedule. The major findings indicated that physical disability did not necessarily relate to an increase in emotional disturbance. The most emotionally disturbing time was the first recurrence of the breast cancer, and the most common disturbance reported in all three treatment groups was in the area of mate role functioning. In addition, adjuvant radiation therapy was a potent source of distress during primary cancer treatment, and at least one-third of all patients in each category reported needing help with household chores.

Psychological response of patients receiving two drug regimens for lung carcinoma.

Seventy-seven patients with small cell lung carcinoma were assigned randomly to two chemotherapy regimens to assess their psychological response to each regimen. One produced less depression and fatigue than the other, despite the absence of differences in tumor response.

A phase I/II trial of etoposide and cisplatin in extensive small cell lung cancer: a cancer and leukemia group B study.

Patients with untreated extensive small cell lung cancer (SCLC) with CALGB performance scores 0-2 were treated with etoposide 200 mg/m2/day on days 1-3 and cisplatin doses of 20, 30, or 35 mg/m2/day days 1-3 in a Phase I/II format. Of the nine patients treated at the 35 mg/m2/day cisplatin dose in the Phase I portion of the study, Grade 4 leukopenia occurred in five patients and Grade 4 thrombocytopenia in four. There were two deaths due to myelosuppression and sepsis. This dose was thus considered the maximum tolerated dose (MTD), and a Phase II trial was then conducted using this treatment program. In the Phase II trial of 39 patients, the objective response rate was 67% (95% confidence interval, 50-81%) with 21% complete responses (CI 9-36%). Median survival was 10.5 months. Grade 4-5 leukopenia was seen in 57% and Grade 4-5 thrombocytopenia in 56%. The MTD defined by this Phase I trial represents a 67-100% increase in etoposide and a 32-42% increase in cisplatin dosage compared to prior studies. The observed objective response rates with this regimen are comparable to studies using conventional doses, but hematological toxicity was higher.

Non-small cell lung cancer at the extremes of age: impact on diagnosis and treatment.

BACKGROUND: Early detection and surgical resection offers the highest likelihood of cure for patients with lung cancer. Patients presenting at the extremes of age may fail to benefit maximally from these interventions. To study the impact of age on stage, histology, symptom, and treatment of patients with non-small cell lung cancer, we undertook a retrospective review. METHODS: One thousand eight hundred two patients with non-small cell lung cancer were identified between 1983 and 1993. Patients were selected by age as less than 45 years (55 patients) and 80 years or more (108 patients), and their medical records were reviewed. RESULTS: Three younger patients (6%) presented with stage I or II disease, yet 15 (32%) underwent thoracic operation. Twenty-seven elderly patients (33%) presented with early stage disease and only 6% underwent operation. The median survival was significantly longer for the younger population with surgically resectable stages of disease (stage I to IIIA) (p < 0.05), whereas no significant difference in survival was seen for the two groups with advanced disease (stage IIIB and IV). CONCLUSIONS: Age significantly affects the presentation and treatment of non-small cell lung cancer patients. Although thoracic operation imparts the greatest survival advantage, this benefit is diminished due to advanced disease in the younger patients and lack of surgical intervention in the elderly.

Cytogenetics of small cell carcinoma of the lung.

Nineteen cell lines derived from various malignant tissues of 15 patients with small cell carcinoma of the lung (SCCL) have been studied. The results showed heterogeneity in all cell lines, with no one consistent abnormality among them. Cell lines from 11 of the patients had minute and double minute chromosomes, and cell lines from 2 patients had abnormally banding regions, designated as ABRs, as distinguished from homogeneously staining regions (HSRs). The latter 2 and several of the former cell lines were derived from specimens taken before the patients were placed on therapy. All but 2 of the cell lines had a constant marker load, consisting of 24%-35% of the complement. Some markers remained stable through months and years of culture life, while other markers came and went. Chromosomes #1, #6 and #11 were most frequently involved in marker formation in the cell lines, and these were compared to similar markers in direct bone marrow preparations. Chromosome #1 markers were of variable structure, whereas #6 and #11 most often took the form of 6q- and 11p+ markers, with breakpoints most frequently at 6q23-25 and 11p11-12. A 3p- marker was found in a minority of cell lines. All of these markers were also found in direct marrow preparations from some patients with SCCL. Nonmonoclonal tumors arose from inoculation of bimodal cell lines into nude mice, but population selection by undetermined mechanism was evident. Cytogenetic parameters showed no positive correlation with hormone production by these cell lines.

Continuous intratumoral infusion of methotrexate for recurrent glioblastoma: a pilot study.

Five patients with documented recurrences of glioblastoma multiforme were given continuous infusions of methotrexate delivered intratumorally using implantable catheters and subcutaneous refillable pumps. A continuous infusion of methotrexate (1 mg/d) was begun with concomitant oral administration of folinic acid. The methotrexate dose was increased every 2 weeks to 3, 10, 30, and, ultimately, 75 mg/d in two patients. Samples of serum and ventricular cerebrospinal fluid (CSF) were obtained to determine the levels of methotrexate and total bioactive folates, and brain tissue was obtained from two patients for determination of methotrexate concentration. The patients survived from 7 to 49 weeks after the implantation of the infusion device. Neither the clinical examination nor sequential radiological studies gave clear evidence of reduction in tumor size. Pneumonia developed in one patient, and mild hepatitis and increased seizure frequency in another. Methotrexate was stable in the delivery system over 12 days, and ventricular CSF reached steady-state levels by 5 days. Steady-state ventricular CSF levels of methotrexate were higher than serum levels in some patients, while the reverse was true in others. Levels of total bioactive folates in the CSF did not increase above the normal range. Methotrexate concentrations were highest at the center of the tumor, but measurable amounts of methotrexate were detectable in all areas of the brain. At autopsy in four patients, variable liquefactive necrosis of the brain tumors was seen, and viable tumor was found at the periphery of the tumor bed. These preliminary results suggest that it is technically feasible to infuse methotrexate into brain tumor cavities, and show that little central nervous system or systemic toxicity was encountered in five patients. Better delineation of the safety and efficacy of this therapeutic approach will require further clinical trials.

Dyspnea, anxiety, body consciousness, and quality of life in patients with lung cancer.

Dyspnea is a common symptom of lung cancer that can impact patient physical, social, and psychological well-being. Study goals were to evaluate quality of life (QOL) and dyspnea in patients with lung cancer and the relationships between QOL, dyspnea, trait anxiety, and body consciousness. Sociodemographic and cancer-related variables (stage, cell type, performance status) were evaluated. One hundred twenty outpatients with stage I-IV lung cancer participated in the study. Patients completed 5 questionnaires assessing QOL, dyspnea, trait anxiety, body consciousness, and pain. Eighty-seven percent of study participants experienced dyspnea. Patients with high dyspnea scores had lower QOL (P = 0.04). Dyspnea was worse in men than in women (P = 0.02), and there was a trend towards older patients reporting more severe dyspnea than younger patients (P = 0.06). There was no difference in dyspnea based on cancer stage, cell type, or performance status. Pain and anxiety scores were higher in patients with high dyspnea (P = 0.02, P = 0.03). Dyspnea was more severe in patients taking opioid analgesics when compared to non-opioids or no pain medications (P = 0.03). No significant association was found between dyspnea, anxiety, and private body consciousness.

Dacarbazine, cisplatin and carmustine, with or without tamoxifen, for metastatic melanoma: 5-year follow-up.

Metastatic melanoma has a grim prognosis. Response rates and survival of patients treated with combination chemotherapy are not superior to single-agent chemotherapy. This study seeks to evaluate the objective response rate and survival of patients with metastatic melanoma treated with multiagent chemotherapy, with or without tamoxifen. Forty-two patients with metastatic melanoma were treated from March 1982 to February 1988 with dacarbazine, cisplatin and carmustine, with or without tamoxifen. An overall objective response rate of 43% was seen (complete response rate 17%; partial response rate, 26%). The response rate was 54% for patients treated with tamoxifen and 25% for patients treated without tamoxifen, but the results did not achieve statistical significance. Median overall survival was 412 days, and was significantly longer in the tamoxifen-treated group. Combination chemotherapy as described in this study is well-tolerated. The observation that tamoxifen appears to impact on survival should be interpreted with great caution due to the deficiencies in the design of the trial and small patient numbers. A randomized trial of this regimen vs single-agent chemotherapy is indicated and is currently being conducted.