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 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The combination of chemotherapy and immunotherapy seems to improve response rate in metastatic melanoma. We investigated the effects on toxicity and immunological effects of a single dose of dacarbacin (DTIC; 850 mg/m2) or cisplatin (CDDP; 100 mg/m2) added to subsequent immunotherapy with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). Twelve patients, who did not respond to IFN-alpha/IL-2 alone were studied. Six received DTIC and IFN-alpha/IL-2, and six received CDDP and IFN-alpha/IL-2. DTIC did not add significant toxicity except for nausea. Significant thrombocytopenia was observed in two patients after CDDP. Although CDDP led to grade 3 nephrotoxicity in two patients, the IL-2-induced fluid retention was less severe than with IFN-alpha/IL-2 alone. Pharmacokinetics of IL-2 were not altered by DTIC, but higher IL-2 serum levels were found in patients with grade 3 nephrotoxicity after CDDP. The IL-2-related induction of secondary mediators (interferon-gamma, tumour necrosis factor-alpha, soluble CD25) was not impaired by chemotherapy and the induction of neopterin was significantly higher after addition of CDDP. One partial response was observed after addition of DTIC to IFN-alpha/IL-2, and one after addition of CDDP. The addition of a single dose of DTIC or CDDP to IFN-alpha/IL-2 is fairly well tolerated and does not abolish induction of secondary mediators. Randomized trials are necessary to test the clinical efficacy.
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PMID:Addition of dacarbazine or cisplatin to interferon-alpha/interleukin-2 in metastatic melanoma: toxicity and immunological effects. 749 66

To define the activity of an individually escalated dacarbazine (DTIC) dose combined with interferon-alpha-2a (IFN), granulocyte-colony stimulating-factor (G-CSF) and ondansetron, 20 patients (pts) with metastatic melanoma were treated with DTIC, ondansetron 8 mg iv, G-CSF 300 micrograms sc and IFN 9 MU sc. Treatment was performed every 21 days to a maximum of 6 courses. DTIC dose was escalated with 250 mg/m2 in case of acceptable toxicity to 1250, 1500 and 1750 mg/m2 in (projected/realized), 14/19, 8/11 and 0/5 pts, respectively. Dose escalation prohibiting toxicities were thrombocytopenia (10 pts), leukopenia (9 pts), and nausea/vomiting (2 pts). Four partial remissions were observed, for a response rate of 20% (95% confidence interval, 6 to 44%). Duration of responses was 1, 2, 3 and 3 months. Median overall survival was 8 months.
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PMID:Dose escalation of dacarbazine combined with interferon alpha-2a, G-CSF and ondansetron in patients with metastatic melanoma. 752 Jun 81

Both chemotherapy and interleukin-2 and/or interferon-alpha produce objective responses in a proportion of advanced malignant melanoma patients. While duration of response to chemotherapy is short, i.e. usually below 4 months, immunotherapy has resulted in a small number of long-lasting remissions in patients with metastatic melanoma. In two consecutive phase II trials in a total of 67 patients, we assessed the potential synergism between both modalities, i.e. chemo- and immunotherapy. Treatment consisted of intravenous (i.v.) carboplatin (CBDCA, 400 mg/m2) and dacarbazine (DTIC, 750 mg/m2) given twice (i.v. bolus over 30 min) at 3-week intervals, or 4 cycles of DTIC (220 mg/m2 i.v. 3 days), cisplatin (DDP, 35 mg/m2 i.v. 3 days), carmustine (BCNU, 150 mg/m2 i.v. cycles 1 and 3) and tamoxifen (TAM, 20 mg oral/daily) at 3-week intervals. Chemotherapy was followed by immunotherapy with combined subcutaneous (s.c.) interleukin-2 (rIL-2) and SC interferon-alpha 2 (rIFN-alpha). Among 40 patients who received a full cycle of chemotherapy with CBDCA/DTIC and sequential immunotherapy, there were 3 (7.5%) complete remissions (CRs) with a median duration of 19 months (range 13-26+). Partial remissions (PRs) were noted in 11 (27.5%) patients with a median response duration of 8 (range 5-14) months. Among 27 patients who received DTIC/DDP/BCNU/TAM and rIL-2/rIFN-alpha, there were 3 (11%) complete remissions and 12 (44.5%) partial remissions. Duration of complete and partial remissions ranged from 9+ to 13+ (median, 11+), and 5 to 15+ (median, 7+) months, respectively. Chemotherapy produced mostly moderate toxicity. Thrombocytopenia was common with the nadir after a median time of 18 days following start of CBDCA/DTIC and DTIC/DDP/BCNU, respectively. 10 patients required transfusion of thrombocytes. Nausea and vomiting due to chemotherapy were well tolerated using concomitant ondansetrone (8 mg i.v.). Immunotherapy was self-administered at home with mild to moderate side effects; malaise, fever, chills, nausea/vomiting, diarrhoea, anorexia and arthralgias were most frequent, but were spontaneously reversible after ending rIL-2/IFN-alpha. A mean 87 and 88% of the projected doses of rIL-2 and rIFN-alpha were administered on either protocol. There were no life-threatening complications and no treatment-related deaths. The sequential combination of chemotherapy and rIL-2 plus rIFN-alpha had at least additive therapeutic activity against metastatic malignant melanoma. The schedules produced long-lasting remissions and were tolerated well overall. These trials substantiate a potential role for low to intermediate dose immunotherapy in maintaining and consolidating therapeutic effects of chemotherapy in metastatic melanoma.
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PMID:Chemoimmunotherapy of advanced malignant melanoma: sequential administration of subcutaneous interleukin-2 and interferon-alpha after intravenous dacarbazine and carboplatin or intravenous dacarbazine, cisplatin, carmustine and tamoxifen. 764 14

A third-generation platinum analogue, zeniplatin, was administered at a dose of 145 mg/m2 intravenously over 60-90 minutes every 21 days as the initial chemotherapy to 21 patients with metastatic melanoma. Prehydration and mannitol diuresis was introduced after the first 7 patients. There were 17 males and 4 females. The median age was 52 (range: 29-81). ECOG performance status was 0 in 10 patients, 1 in 8 patients and 2 in 3 patients. Major disease sites were lymph nodes, skin, lung, liver, and bone. Patients received a median of 2 cycles (range: 1-7). Two patients achieved partial responses. One with nodal disease progressed after 166 days and the other with buccal mucosal disease after 142 days. A third patient showed partial regression of nodal disease but developed cerebral metastases. Gastrointestinal toxicity included WHO grade 3 vomiting in 8 patients and nausea in 2. Antiemetics were used, but ondansetron was not available. WHO grade 3 hematologic toxicities included neutropenia in 8 patients and anemia and thrombocytopenia in 1 patient. Thrombocytosis was seen in 35% of courses. Dosage reduction was required in 15% of courses and escalation in 5% of courses. Three patients developed phlebitis related to the infusion. One patient developed a reversible rise in serum creatinine, but, unlike other studies, no severe nephrotoxicity was reported. Zeniplatin demonstrated only modest activity in melanoma with significant gastrointestinal and hematologic toxicity.
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PMID:A phase II trial of zeniplatin in metastatic melanoma. 784 60

Interleukin (IL-4) is a pluripotent cytokine that stimulates proliferation of activated T-cells and has antineoplastic activity against human renal tumors in animal systems. In phase I trials, IL-4 could be tolerated at doses up to 20 micrograms/kg, with dose-limiting toxicities consisting of fever, fluid retention, nasal congestion, and mucositis. We report the results of two separate Phase II trials of IL-4 in 30 patients with metastatic malignant melanoma and 19 patients with advanced renal cancer. IL-4 was administered intravenously every 8 h for 14 doses in two 5-day courses separated by a 9-day interval. The first 27 patients were treated at a dose of 800 micrograms/m2, but after three of these patients developed cardiac toxicities, the dose was decreased to 600 micrograms/m2. One complete response occurred in a patient with metastatic melanoma (duration > or = 30 months). No responses were seen among the patients with renal cancer. The most frequent side effects were fever, nausea, malaise, nasal congestion, and diarrhea. Reversible hepatic and renal dysfunction were also common. Hypotension was infrequent, but transient weight gain due to fluid retention was common. The major life-threatening toxicities were cardiac and gastrointestinal. Suspected cardiac ischemia was observed in two patients, pericarditis in one, and arrhythmias in two. Three patients had major upper gastrointestinal bleeding without evidence of local tumor. We conclude that IL-4, when given as a single agent on this schedule at maximum tolerated dose, does not possess meaningful activity in renal cancer or melanoma.
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PMID:Phase II studies of recombinant human interleukin-4 in advanced renal cancer and malignant melanoma. 813 48

A phase II study of the synthetic polyelectrolyte Carbetimer 6500 mg/m2 i.v. daily for five days every 21-day cycle was conducted in patients with metastatic melanoma. No responses were seen in 18 evaluable patients. Two patients had stable disease for five months. Toxicity was generally manageable and included mild hyperphosphatemia, mild proteinuria, fatigue, pain at the injection site, and nausea. Carbetimer is inactive in metastatic melanoma at this dose and schedule.
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PMID:Phase II trial of carbetimer in metastatic melanoma. 826 38

Two cases of metastatic malignant melanoma of the lower limb who were treated successfully with hyperthermic isolated limb perfusion are reported. One patient was infused with cisdiammine (1.1-cyclobutanedicarboxylate) platinum (II) (carboplatin, Paraplatin, Bristol-Myers Squibb Company, New Jersey, USA), and the other was infused with human natural beta-interferon (Feron, Toray, Tokyo, Japan), via the external iliac artery. The first case showed a remarkable suppression of the growth of multiple metastatic melanoma nodules associated with numerous melanophage infiltrations, as shown histopathologically after the operation. The patient's serum level of 5-S-cysteinyl dopa decreased for the two months following the treatment. In the second case, new formation of metastatic melanoma nodules was completely suppressed for up to 12 months following the operation. Analysis of immunological parameters showed that the number of peripheral CD8+ lymphocytes gradually and constantly increased after the operation, while that of CD4+ lymphocytes transiently increased and then returned to the pre-operative level. Natural killer activity transiently decreased to a slight degree 4 days after the operation and then returned to the pre-operative level 21 days after the operation. Side effects, such as nausea, vomiting and leg discomfort, were seen in the patient (Case 1) treated with carboplatin, but were completely reversible. These results suggest that hyperthermic isolated limb perfusion with concomitant infusion of carboplatin or beta-interferon is effective in suppressing the growth of metastatic malignant melanomas of the lower limb.
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PMID:Two cases of metastatic malignant melanoma of the lower limb treated with hyperthermic isolated limb perfusion and concomitant infusion of either carboplatin or beta-interferon. 872 Feb 52

The toxicity and clinical response to treatment with the combination of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in patients with metastatic melanoma was evaluated. From May 1993 through February 1994, 20 patients were treated with 24 courses of IFN-gamma with or without IL-2. A 7-day course of subcutaneous IFN-gamma alone was administered to cohorts of two or three patients each at doses of 0.1, 0.2, or 0.3 mg/m2. Thirteen patients received escalating doses of IFN-gamma between 0.2 and 0.5 mg/m2 followed by the intravenous (i.v.) administration of IL-2 (720,000 IU/kg) given three times a day. A treatment course consisted of two cycles (maximum of 15 doses of IL-2 per cycle) separated by a 10-day interval. Five additional patients were treated with five courses of IFN-gamma, IL-2, and tumor-infiltrating lymphocytes (TILs). All patients treated had the diagnosis of metastatic melanoma. The maximal tolerated dose of subcutaneous IFN-gamma was established at 0.3 mg/m2 with dose-limiting hepatotoxicity. Immunohistochemistry analyses showed detectable upregulation of MHC class I alleles in one (8%) of 12 patients. Two of 20 patients who received the combination of IFN-gamma and IL-2 had responses, one partial and one complete response. The duration of response was 7 months for the partial response and 12 months for the complete response. IFN-gamma was tolerated with minimal side effects of nausea, vomiting, malaise, and decreased hematopoiesis. No increased toxicities were found with the combination treatment, as compared with IL-2 alone. One death occurred on the third day of treatment with IFN-gamma alone from hemorrhage into brain metastases. There were no responders in the five patients who received the combination treatment of TIL, IL-2, and IFN-gamma. From these findings, we conclude that further studies looking at this combination treatment are not warranted.
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PMID:Combination therapy with interferon-gamma and interleukin-2 for the treatment of metastatic melanoma. 885 24

The therapy of metastatic melanoma is limited by poor responses to known chemotherapeutic agents. The report of Mulder et al. (Proc ASCO 1992; 11: 347) raised the possibility of the known interaction between 5-fluorouracil and interferon-alpha2a improving response rates in melanoma. This study was designed to examine the effects of 5-fluorouracil plus interferon-alpha2a alone without the confounding effects of dacarbazine. Doses were chosen based on the earlier study rather than the higher doses used in colon cancer. Therapy for metastatic melanoma with 5-fluorouracil and interferon-alpha2a is manageable in terms of toxicity. The major toxicities were lethargy, nausea/anorexia and flu-like symptoms. These were thought to be primarily attributable to interferon-alpha2a. Only one case of severe diarrhoea occurred. The response rate of 14% is similar to the reported results of interferon-alpha2a treatment alone. On these data, there is no evidence of synergy using this dose and schedule.
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PMID:Recombinant interferon-alpha2a plus 5-fluorouracil for the treatment of metastatic melanoma. 946 25

Inspired by the high response rates achieved with the DBCT regimen (dacarbazine [DTIC], carmustine [BCNU], cisplatin and tamoxifen [TAM]), we administered the nitrosourea compound fotemustine, cisplatin and TAM (FCT regimen) to 69 patients with metastatic melanoma. Fotemustine (100 mg/m2) and cisplatin (100 mg/m2) were administered every 4 weeks, preceded by TAM 160 mg daily for 7 days from the second course onwards. Pharmacokinetic blood sampling was performed in 14 patients during the initial two cycles to compare the pharmacokinetic behaviour of fotemustine with or without TAM. Previous chemo- or radiotherapy was allowed, and patients with brain metastases or concomitant other malignancies were included. Four complete and 11 partial responders were observed among 66 evaluable patients, yielding a response rate of 22.7% (95% confidence interval 12.9 32.5%). The median survival time was 6.4 months (range 0.1-52+ months). The main toxicities were thrombocytopenia, protracted nausea/vomiting and ototoxicity. Renal toxicity was generally mild, but possibly contributed to two deaths. Seven patients experienced deep venous thrombosis during the study. TAM had no influence on the pharmacokinetics of fotemustine. The activity of the FCT regimen was clearly inferior to that initially reported with DBCT treatment. However, a recent publication concludes that the latter achieves a considerably lower response rate when administered to a larger patient group. We believe our results reflect the true activity of FCT and similar regimens when administered routinely to unselected patients. Considering the number of potentially serious side effects, we cannot recommend the moderately active FCT regimen as a palliative treatment option for melanoma patients.
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PMID:Clinical experience of fotemustine, cisplatin and high dose tamoxifen in patients with metastatic malignant melanoma. 991 19


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