Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixteen patients with Hodgkin's (10) and non-Hodgkin's (6) lymphoma were treated by the "ABCD scheme", which is a combination of adriamycin (25-30 mg/m2 day 1), bleomycin (15 mg day 1-5), CCNU (60 mg/m2 day 1) and DIC (90-100 mg/m2 day 1-5). 15 results are evaluable and included 5 complete remissions, 5 partial remissions, 2 stabilizations, 2 progressions and 1 early death (remission rate: 66%). 45 ABCD courses were given. 8 patients received more than one course (maximum 7 courses). Toxicity was tolerable and consisted mainly of myelodepression, nausea, vomiting and muco-cutaneous alterations. Two patients died following toxicity, one from myelosuppression and the other from interstitial pulmonary fibrosis. The results suggest that this combination can be useful where the usual chemotherapy combination fails.
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PMID:[Simultaneous combination of adriamycin, bleomycin, cyclohexyl-chloroethyl nitrosourea with dimethyl-triazeno imidazole carboxamide in the treatment of Hodgkin's lymphoma]. 6 45

Thirty-seven patients with advanced Hodgkin's disease have been treated for greater than or equal to 3 months with a protocol consisting of alternate monthly courses of MOPP (mechlorethamine, Oncovin [vincristine], procarbazine, and prednisone) and ABDV (adriamycin, bleomycin, DTIC, and vinblastine) with local radiotherapy (RT) to areas of originally bulky disease. This therapy produced CR in 19 of 19 previously untreated patients (100%), eight of nine previously treated with RT (89%), and six of nine previously treated with RT and MOPP (67%). The remaining patients are all PRs tending toward CR status. The median time to CR was 3.0 months. The median time in remission to date for the previously untreated patients is 8+ months (2+-14+). After an induction period of eight cycles of chemotherapy patients are maintained on alternate-month treatment continuing the alternating sequence. During this phase three patients have experienced reappearance of disease (one recurrence, one possible second primary lymphoma, and one recurrence in a patient whose original diagnosis is in doubt). The regimen has been well tolerated. All patients were treated as outpatients. Alopecia and neurotoxicity were mild and myelosuppression was moderate. Clinically significant cardiopulmonary toxicity has been limited to mild radiation pneumonitis in one patient and bleomycin pneumonitis which cleared during prednisone in a second patient.
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PMID:Eight-drug combination chemotherapy (MOPP and ABDV) and local radiotherapy for advanced Hodgkin's Disease. 6 21

One hundred twenty patients with metastatic malignant melanoma were randomized to receive either cyclophosphamide, 600 mg/m2 IV, on day 1 plus DTIC 200 mg/m2 IV days 1 through 5, or the same chemotherapy plus C. parvum 5 mg/m2 IV on day 8 and day 15. Therapy was repeated every 21 days. Although responses were observed in 13.8% of patients on cyclophosphamide plus DTIC versus 25.5% of patients on cyclophosphamide plus DTIC plus C. parvum, the median duration of remission was 15.6 weeks on chemotherapy and 13.0 weeks on chemotherapy plus C. parvum. Furthermore, survival was similar on both regimens (6.1 months versus 5.7 months, respectively). Favorable prognostic factors included metastatic disease confined to skin or lymph nodes (33% responses), performance status greater than 70% (24% response rate), and administration of three or more courses of chemotherapy (31% response rate). The dose limiting toxicity was myelosuppression, which was equal on both regimens. Chills and fever were common in response to C. parvum, and, rarely hypotension, cyanosis, or immune nephritis was observed. The addition of C. parvum to chemotherapy with cyclophosphamide plus DTIC is not recommended.
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PMID:Cyclophosphamide plus 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) with or without Corynebacterium parvum in metastatic malignant melanoma. 38 76

Considerable progress recently has been made in the systemic chemotherapy of disseminated skin neoplasms. Several agents are particularly useful in this regard: the nitrosoureas, methotrexate, actinomycin D, and dacarbazine. This paper reviews their pharmacologic disposition in man. The nitrosoureas have short plasma half-lives; however, they are extensively degraded to metabolites that persist in the body, and are only slowly excreted. Highly soluble in lipids, the nitrosoureas penetrate significantly into the central nervous system. Actinomycin D is only minimally metabolized in vivo; its elimination from the plasma shows a prolonged slow phase with a half-life of 36 hours; but its excretion is even slower than expected about 30% in a week. A potent inhibitor of dihydrofolate reductase, methotrexate exhibits a multiphasic plasma disappearance, and accumulates in tissues with high dihydrofolate reductase activities. At the normal therapeutic dosages, methotrexate is eliminated by the kidneys as the unchanged drug; appropriate dosage modifications are mandatory if renal function is compromised. Dacarbazine has a relatively short plasma half-life, and is rapidly excreted partly as the unchanged drug; it undergoes extensive biotransformation in the body. Like other antitumor agents, these drugs may cause gastrointestinal toxicities and myelosuppression; in addition each drug can have its own individual organ toxicity.
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PMID:Clinical pharmacology of systemic chemotherapeutic agents in skin neoplasms. 73 Apr 48

The effects of adriamycin were compared to a combination program of methyl-CCNU and imidozole carboxamide (DTIC) in 44 patients with disseminated malignant melanoma. There were objective clinical responses in 6 of 21 patients with the combination of DTIC and methyl-CCNU who received this program as primary treatment and none in 23 patients receiving adriamycin as primary treatment. Secondary responses were not observed with either treatment regimen. Toxicity with the combination program included leukocyte depression (less than 3,000/cu mm) in 25% and platelet depression (less than 100,000/cu mm) in 40% compared to 52% leukocyte depression and 16% platelet depression after adriamycin. There were no responses after the combination treatment program in the absence of myelosuppression. There was nausea and vomiting in virtually all patients, which was moderately severe in one third of the patients receiving the combination and in only 10% of those receiving adriamycin. Alopecia developed in all who received adriamycin but in only 15% of the combination treatment group. The combination treatment response of 28% was of the same order as most response rates previously reported in this disease. This randomized controlled clinical trail found adriamycin without clinical benefit and not worthy of further trial in patients with disseminated malignant melanoma.
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PMID:Clinical comparison of adriamycin and a combination of methyl-CCNU and imidazole carboxamide in disseminated malignant melanoma. 77 89

Combination chemotherapy with adriamycin and DTIC was used in 102 evaluable patients under 15 years of age who had previously treated metastatic solid tumors. Responses, defined as 50% or more reduction in all tumor masses, occurred in 10 out of 27 patients with neuroblastoma, 3 out of 8 patients with Wilms tumor, 7 out 15 patients with Ewing sarcoma, 2 out of 6 patients with osteosarcoma, 5 out of 13 patients with rhabdomyosarcoma, and 15 out of 33 patients with miscellaneous tumors which included a patient who had a complete regression of an extensive juvenile angiofibroma. Response rate to combination chemotherapy with adriamycin and DTIC in patients with Ewing sarcoma was significantly superior to the response rate obtained with adriamycin alone in another Southwest Oncology Group Study. Major toxicity included nausea, vomiting, myelosuppression, high incidence of pneumocystis carinii pneumonia (5 patients) and congestive heart failure (4 patients). There was 7 drug-associated deaths due to sepsis (1), pneumocystis carinii pneumonia (4), and congestive heart failure (2).
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PMID:Combination chemotherapy with adramycin (NSC-123127) and dimethyl triazeno imidazole carboxamide (DTIC) (NSC-45388) in children with metastatic solid tumors. 95 60

From favorable results with 254-S, a new cisplatin analogue, single administration, we have conducted a clinical study to investigate the efficacy of combination of 254-S, ifosfamide and peplomycin, each of which has a different dose limiting factor. A total of 45 patients, including 22 patients with stage III and IV cervical cancer and 23 cases with recurrent cervical cancer, were treated with at least two courses of 254-S (100mg/m2, iv. Day 1), ifosfamide (1,500mg/body, iv. Day 1-5) and peplomycin (5mg/body, im. Day 1-6), and tumor response was evaluated clinically and by CT scanning. The response rate obtained in patients with advanced disease was 81.8% (PR = 17, CR = 1) and that in cases with recurrence was 60.9% (PR = 12, CR = 2). Myelosuppression was the dose limiting factor. In the 121 courses, grade 3 and 4 of leucopenia and thrombocytopenia were observed with an incidence of 44% and 32%, respectively and DIC occurred in 3 cases with poor PS though they recovered after reducing the 254-S dose to 80 mg/m2. The other toxicities were mild except for alopecia. Anaphylaxia was observed in a case at the second administration though the patient recovered in 15 minutes. There was no death. As to prognosis, a significant prolongation of survival period was observed in recurrent cases and 4 cases are alive (NED) after one and a half year. In the advanced cases, until now 3 cases of stage IV have died from the disease. We have concluded that this regimen is effective as a neoadjuvant chemotherapy for advanced cervical cancer and useful for the treatment of recurrent cervical cancer.
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PMID:[Combination chemotherapy with 254-S, ifosfamide and peplomycin for advanced or recurrent cervical cancer]. 137 59

Fifty-six patients with measurable advanced soft-tissue sarcomas were treated with epirubicin, 90 mg/m2 intravenously on day 1, and DTIC, 250 mg/m2 intravenously on days 1-5, with the entire regimen repeated every 3 weeks. The overall response rate in 52 evaluable patients was 48% with 9 complete remissions. Noncardiac toxicity was limited predominantly to vomiting, alopecia and myelosuppression. Laboratory evidence of cardiotoxicity [greater than or equal to 20% decrease in left-ventricular ejection fraction (LVEF) from the baseline value] was observed in 4 out of 39 patients who had at least two determinations of LVEF, at a median dose of 1,305 mg/m2. Two patients had clinical congestive heart failure at cumulative dose of 1,440 and 1,620 mg/m2. These findings suggest that the combination of epirubicin and DTIC is an active regimen in soft-tissue sarcomas, and provide further evidence that epirubicin is a doxorubicin analogue with reduced cardiac toxicity, but preserved efficacy in this disease.
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PMID:Epirubicin and DTIC (EDIC) for advanced soft-tissue sarcomas. 202 3

Based on the report of some activity of combination therapy with dacarbazine (DTIC) and interferon alpha-2a (rIFN alpha-2a) in disseminated melanoma, we conducted a phase II study to determine the feasibility and efficacy in a large series of patients. DTIC was administered in 79 patients at the dose of 800 mg/m2 every 3 weeks and rIFN alpha-2a was given daily at the dose of 9 X 10(6) IU for the first 10 weeks and three times a week thereafter. Among the 75 evaluable patients, 25% achieved an objective response, with 8% complete and 17% partial remissions. The regression occurred within a mean time of 1.9 +/- 1.03 months from starting therapy and the mean duration of response was 8.2 +/- 4.2 months. The major side effects were vomiting, anorexia, fever, fatigue, and myalgia. There was one death related to sepsis after myelosuppression. In the other patients bone marrow and liver toxicities were not remarkable. Our data reveal that a combination regimen of rIFN alpha-2a with a cytotoxic agent has some therapeutic activity in the management of advanced malignant melanoma.
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PMID:Phase II study of interferon alpha-2a and dacarbazine in advanced melanoma. 222 Jun 60

In this phase II trial, 105 eligible patients with no prior chemotherapy and advanced sarcoma received doxorubicin, ifosfamide, and dacarbazine (DTIC) with mesna uroprotection (MAID). Starting doses of these drugs were 60, 7,500, and 900 mg/m2 divided over 72 hours by continuous infusion, respectively. Mesna was given for 84 to 96 hours at 2,500 mg/m2/d. Myelosuppression was dose limiting, causing the only toxic death (sepsis). Nonhematologic toxicity consisted predominantly of anorexia and vomiting. Severe mucositis, macroscopic hematuria, renal tubular acidosis, renal failure, and CNS toxicity occurred in less than 5% of cycles. No cardiotoxicity was detected. The overall response rate (10% complete response [CR]) was 47% (95% confidence intervals, 5% to 18% and 37% to 57%, respectively). Most responses (approximately 70%) were observed within two cycles. Median times to progression were 10 and 9 months, respectively. Histologic high tumor grade, lesions less than 5 cm, and less than 1 year from diagnosis to study entry correlated with the probability of response. The median survival was 16 months. Time from diagnosis to study entry, performance status, and extent of disease, but not histologic grade, correlated with survival. Following CR, two patients remain disease-free at 32 and 16 months. Of the 15 additional patients rendered disease-free with surgery, two remain disease-free at 30 and 18 months with no further therapy. While most relapses occurred in sites of prior involvement, death from CNS metastases occurred in 11 of the 80 patients with high-grade sarcomas, of whom seven were still responding systematically (three complete responders). Because of its substantial response in this phase II trial, the MAID regimen is being compared with doxorubicin and DTIC alone in advanced sarcomas and to observation in the adjuvant treatment of high-grade sarcomas in randomized trials.
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PMID:Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. 250 90


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