Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on results of a phase I study demonstrating antitumor activity of taxol in patients with melanoma, 34 patients with documented metastatic melanoma received taxol, 250 mg/m2, as a 24-hours infusion, repeated every 21 days, in this phase II study. All patients received premedication with dexamethasone, diphenhydramine and cimetidine. Four patients experienced anaphylactic reactions and stopped treatment. Other significant toxicity of this drug included short-lived but severe neutropenia (less than 1,000/mm2) and peripheral neurotoxicity. Four of 28 evaluable patients demonstrated objective response (14%) (confidence interval, 4%-33%) including 3 complete responses and 1 partial response. Two complete responders are continuing at 25+ and 38+ months after achieving CR. Minor evidence of anti-tumor activity was noted in five additional patients. Taxol has significant activity in melanoma and should be further studied in combination with other agents in this disease.
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PMID:A phase II study of taxol in patients with malignant melanoma. 167 65

Cisplatin and dacarbazine are used widely in the treatment of metastatic melanoma. To evaluate high-dose cisplatin and dacarbazine, 32 patients with metastatic melanoma were treated with cisplatin 50 mg/m2 and dacarbazine 350 mg/m2 daily for three days repeated at 28-day intervals. Their median age was 43.5 years (range, 25 to 73 years), and their median Karnofsky performance status was 80% (range, 70% to 100%). Measurable and evaluable disease sites (number of patients) included lymph nodes (22), lung (17), soft tissue (16), liver (13), bone (seven), spleen (four), adrenal gland (three), skin (three), and other sites (five). Patients received a median of two cycles of therapy (range, one to eight cycles). Thirty patients were evaluable for response. No complete responses were observed. Five patients had a partial response (17%; 95% confidence interval, 3% to 30%) for 16+, 12+, 7, 6.5, and 3 months. Responding sites of disease included lymph nodes (five of 22), lung (three of 17), and soft tissue (two of 16). Hematologic toxicity (Grade greater than or equal to 3) included neutropenia (16 of 32 patients, 30 of 90 cycles), thrombocytopenia (eight of 32 patients, 12 of 90 cycles), and anemia (five patients). Nine episodes of neutropenia and fever were seen in four patients; two had bacteremia. Nonhematologic toxicity (Grade greater than or equal to 3) included hypotension (two patients), nausea and vomiting (four), neuropathy (two), ototoxicity (four), and hypomagnesemia (nine). The low objective response rate and severe toxicity of this regimen preclude its standard use in patients with metastatic melanoma. A review of cisplatin-based therapy in metastatic melanoma suggests that there is no dose-response relationship. The use of high-dose cisplatin (greater than 100 mg/m2) in the treatment of metastatic melanoma is not recommended.
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PMID:A phase II trial of high-dose cisplatin and dacarbazine. Lack of efficacy of high-dose, cisplatin-based therapy for metastatic melanoma. 187 74

Taxol is an investigational new drug which is currently undergoing Phase II evaluation in various tumors. It is a plant alkaloid extracted from the western Yew, Taxus brevifolia. In this study, patients with metastatic melanoma who were previously untreated, received Taxol at a starting dose of 250 mg/m2 delivered as a continuous intravenous (IV) infusion over 24 hours, at 3-week intervals. All patients were premedicated with oral dexamethasone and IV diphenhydramine hydrochloride as prophylaxis against allergic reactions. Three of 25 patients had a partial response (PR) for a response rate of 12% (CI, 3%-31%). In addition four patients had objective regression of tumor that failed to qualify for a PR but these responses were as durable, lasting 6 to 17 months. No patient experienced acute allergic reactions. The major toxicity of Taxol was neutropenia requiring dose reduction to 200 mg/m2 in a majority of the patients. Our data confirm that Taxol has definite although limited activity against metastatic melanoma.
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PMID:A phase II trial of taxol in metastatic melanoma. 197 Sep 48

Thirty patients with documented metastatic melanoma were randomly assigned to receive recombinant DNA-produced gamma-interferon (specific activity approximately, 20 MU/mg) intravenously (IV) over either two or 24 hours at dosages of 3, 30, 300, 1,000, or 3,000 micrograms/m2. Objective toxicity resembled that of alpha-interferon and included fever, chills, myalgias, headache, and fatigue. Neutropenia, elevations in liver enzymes, tachyarrhythmias, and CNS changes also were noted. Dose-limiting toxicity included neutropenia, liver enzyme abnormality, constitutional symptoms, and a change in mental status. The incidence of toxicity was qualitatively similar in both two- and 24-hour treatment arms, but was quantitatively more severe in the 24-hour continuous infusion arm. Maximum tolerated dose was 1,000 micrograms/m2 in both schedules. Pharmacokinetic studies showed a half-life of six to nine hours. One patient had a complete response after two cycles of therapy and an additional patient entered partial remission after three cycles. Recombinant gamma-interferon (rIRN-gamma) is tolerated at dosages of 1,000 micrograms/m2 administered daily either by two or 24 hour infusion for 14 days in patients with metastatic melanoma. The responses documented in this early trial warrant further evaluation for the treatment of metastatic melanoma.
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PMID:A randomized phase I/II study of continuous versus intermittent intravenous interferon gamma in patients with metastatic melanoma. 311 86

Thirteen patients with metastatic melanoma and ten patients with advanced renal cell cancer (RCC) received interferon alfa-2a (Roferon-A) and vinblastine. In melanoma the interferon dose was 3-9 million IU i.m., escalated daily for 10 weeks, and in RCC the dose was 18 million IU three times a week i.m. The dose of vinblastine was 0.075-0.15 mg/kg every third week i.v. One of the ten evaluable patients with melanoma had partial remission (PR; 11%) and three presented no change (NC). Three of seven evaluable patients with renal cell carcinoma had PR (43%) and three NC. Duration of the remission was 10 months in the melanoma patients and 7+, 10+, and 7+ in the RCC patients. The three times a week schedule was better tolerated. The most common side effects were fever, fatigue, loss of taste, weight loss, and neutropenia. On the basis of these results it can be concluded that in melanoma the combination of daily administration of interferon and vinblastine is not effective, whereas in renal cell cancer interferon and vinblastine treatment given three times a week seems to be favorable.
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PMID:Combined interferon and vinblastine treatment of advanced melanoma and renal cell cancer. 318 Jan 44

A randomized phase II study of AMSA (amsacrine) alone and AMSA combined with DTIC (dacarbazine) was carried out in 31 and 39 patients with metastatic melanoma respectively. AMSA was used at a starting dose of 40 mg/m2/day X 3 days with escalation to 50-60 mg/m2/day X 3 days in 8 pts. For AMSA + DTIC the starting dose was: AMSA 30 mg/m2/day X 3 days; DTIC, 800 mg/m2 X 1 day. Additionally, seven pts received AMSA in a similar dose schedule but DTIC was used in a 5-day schedule of 250 mg/m2/day. Twenty-five patients were evaluable for response in the AMSA group and 36 in the AMSA + DTIC group. The objective response to AMSA included 1(4%) partial response compared with 11 complete or partial responses (30%) with AMSA + DTIC therapy. The median lowest absolute granulocyte count was 1100/microliters in AMSA group compared with 1000/microliters in the AMSA + DTIC group. Severe neutropenia of less than 500 granulocytes/microliter was observed in 5 pts in the AMSA group compared with 13 pts in the AMSA + DTIC group. We concluded that AMSA has no significant activity against melanoma, although the combination of AMSA + DTIC seemed to be more active than DTIC alone.
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PMID:Phase II study of AMSA alone and in combination with DTIC in patients with metastatic melanoma. 341 Jun 67

In two phase I-II trials, 33 patients were given recombinant interferon alpha-2 daily at dosages of 3, 10, 30, 50, or 100 MU/d for up to 4 weeks by intramuscular or intravenous routes. Dose-limiting toxicities, including neutropenia, elevated hepatocellular enzyme levels, fatigue, and disturbed mentation, correlated with differing serum pharmacokinetics of interferon in the two trials. In the intramuscular study, dose-limiting toxicity occurred at all dosages greater than 10 MU/d, at a median of 6 to 9 days of treatment. In the intravenous dose-study, limiting toxicity was seen only at dosages of 100 MU/d, at a median of day 8. Twenty-three patients had metastatic melanoma and 4 had objective partial or complete responses at dosages of 10 to 50 MU/d in the first month. Two patients with complete responses are free of tumor after 2.5 years of follow-up. A fifth patient had delayed complete regression, requiring 1 year to achieve maximum response, but remains free of disease at 26 months since entry to the trial. Interferon had antitumor activity against melanoma by both routes tested, at dosages of 10 to 50 MU/d.
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PMID:Comparison of intramuscular and intravenous recombinant alpha-2 interferon in melanoma and other cancers. 400 87

A phase II study using vindesine (3 mg/m2 by slow intravenous push at seven to 14 day intervals) was carried out in 42 patients with metastatic melanoma. There was one complete remission (2.5%) of greater than 12 months duration; seven partial remissions (17.5%) of two, three, three, four, five, six and eight months duration; 11 with no change (27.5%) of one to 10 months duration; and 21 (52.5%) patients with increasing disease. Toxicity included neutropenia, neurotoxicity, phlebitis and cellulitis at the site of injection, alopecia, fever and chills, myalgias, and gastrointestinal toxicity. It was concluded that vindesine does have activity in some patients with metastatic malignant melanoma. Further studies in previously untreated patients are warranted.
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PMID:Vindesine in patients with metastatic malignant melanoma: a Southwest Oncology Group study. 670 19

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

40 patients with symptomatic metastatic melanoma were treated with procarbazine, vincristine and lomustine (POC). 4 patients had received chemotherapy previously. Responses were seen in 8 patients (20%), 4 of whom had a complete remission. All responding patients had some tumour shrinkage after one cycle. The median duration of response was 27 weeks, with 2 patients remaining in complete remission at 6 and 6.5 years. The median survival for the whole group was 22 weeks, whilst that of the responding patients was 35 weeks. Using conventional anti-emetics, the principal toxicities were nausea and vomiting, severe in 15% of cycles. Other nonhaematological toxicity was uncommon. Neutropenia (WHO grade 3 or 4) occurred in 11% of cycles and thrombocytopenia in 8%. The response rate of metastatic melanoma to POC chemotherapy was similar to other cytotoxic regimens though toxicity, other than nausea and vomiting, was minimal. The rapid response allows patients with unresponsive disease to be identified early, avoiding continuing toxicity.
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PMID:Phase II trial of procarbazine, vincristine and lomustine (POC) chemotherapy in metastatic cutaneous malignant melanoma. 785 2


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