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)

Urinary alkalinization with oral sodium bicarbonate has decreased the incidence of acute nephrotoxicity and subsequent myelotoxicity in 18 adults receiving high-dose methotrexate with calcium leucovorin rescue (MTX-LCV) weekly in doses of 1-7.5 g/m2. Close monitoring of 24-hour serum creatinine and MTX levels can predict patients at risk for serious toxicity. By a prompt (24-36 hours) increase in the LCV dose rate, hematologic and biochemical evidence of myelosuppression has been prevented. Kinetic parameters in serum and lumbar cerebrospinal fluid (CSF) were studied in two patients following iv injection of 3 and 7.5 g/m2 respectively. Lumbar CSF MTX concentrations greater than 1 muM are achieved. The half-life of MTX in the CSF (11.95 hours) is twice as long as the serum half-life. In the presence of carcinomatous meningitis, further delay in the clearance of MTX from the CSF was seen. With weekly MTX-LCV, there have been four objective responses in six patients with non-Hodgkin's lymphoma in CNS relapse, including complete regression in two. It is suggested that therapeutic concentrations can be achieved in the central nervous system following MTX-LCV.
Cancer Treat Rep 1977 Jul
PMID:Weekly methotrexate-calcium leucovorin rescue: effect of alkalinization on nephrotoxicity; pharmacokinetics in the CNS; and use in CNS non-Hodgkin's lymphoma. 1 82

Eighty-three patients with Stage II or Stage III germinal neoplasia of the testis and 7 patients with extragonadal primary tumors were treated with bleomycin plus vinblastine, or a five-drug program, bleomycin plus cyclophosphamide, vincristine, methotrexate, and 5-fluorouracil. Of the 70 Stage III patients, there were 53 responses (75%), 22 complete and 31 partial. The mean survival of the complete responders is 100+ weeks, with 3 dead. The mean survival of the partial responders and nonresponders is 38 weeks and 33 weeks, respectively. There is a highly significant difference between complete responders vs. partial and nonresponders (p less than 0.01). Thirteen patients with nonmeasurable disease (Stage II and Stage III postresectional status) but at great risk to develop widespread metastasis were treated prophylactically after conventional therapy. Nine continue in complete response to 36 months. The 7 extragonadal primary patients showed 4 partial responses, none complete. Major toxicity was myelosuppression and also bleomycin pneumonitis in 5 of the 90 evaluable patients.
Cancer 1975 Aug
PMID:Bleomycin combination chemotherapy in the management of testicular neoplasia. 5 Aug 69

One hundred eighty-nine patients received a four-drug combination consisting of cyclophosphamide, Oncovin (vincristine), methyl CCNU, and bleomycin (COMB), according to three different drug regimens, performed sequentially. Of the 189, 62 had a partial response (33%) including 11/33 with squamous lung cancer, 11/32 with squamous carcinoma of the head and neck, 13/15 with oat cell carcinoma of the lung, and 7/41 with malignant melanoma. The response rate for patients with squamous lung or head and neck cancer appeared to be higher at weekly bleomycin doses of 30 and 60 mg (15/33 = 45%), compared to a weekly bleomycin dose of 15 mg (7/32 = 25%). A median survival from treatment of 30 weeks was observed in oat cell carcinoma, which represents considerable prolongation over that expected from supportive care alone or single-agent chemotherapy. Toxicity included: 1) myelosuppression, resulting in hospitalization for antibiotics in 20% of patients; 2) probable bleomycin lung damage in 4% of patients; and 3) dose-limiting vincristine neuropathy in 11%. The combination of twice-weekly vincristine and bleomycin for more than 6 weeks produced a disturbing "debilitation syndrome," characterized by weakness, anorexia, weight loss, and apathy. The encouraging response rate suggests a future role for these drugs in combination, especially for vincristine and bleomycin, with other agents showing activity in squamous and oat cell carcinoma. Toxicity precludes recommendation of this combination, in the regimens tested, for broader Phase III studies.
Cancer 1975 Aug
PMID:COMB (cyclophosphamide, oncovin, methyl-CCNU, and bleomycin): a four-drug combination in solid tumors. 5 Aug 70

Utilizing the stathmokinetic principle of timed vincristine and bleomycin, we combined these two agents with Mitomycin-C. The dose schedule included vincristine 0.5 mg/m2 intravenously (i.v.) geginning on day 1 and repeated twice weekly for 12 weeks; each injection was followed in 6-12 hours by bleomycin 6 mg/m2 for 12 weeks. Mitomycin-C was administered as a 20 mg/m2 bolus beginning on day 2 and repeated at 6-week intervals. Thirty patients were entered into this study, 27 were fully available for response. Thirteen patients (48%) met criteria of response (greater than 50% reduction in volume of measurable tumor). Significant myelosuppression resulted from this therapy. Median leukopenia nadir was 3.8 X 10(3) cells/mm3 and median thrombocytopenia nadir was 116 X 10(3) cells/mm3. Additional toxic reactions included anemia, lassitude, anorexia, peripheral neuropath fever, and skin rash. Despite significant, but manageable, toxicity, this combination appears to represent an improvement in the chemotherapy of a traditionaly refractory solid tumor.
Cancer 1976 Dec
PMID:Phase II study of mitomycin-C, vincristine, and bleomycin in advanced squamous cell carcinoma of the uterine cervix. 6 14

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.
Cancer Treat Rep 1976 Sep
PMID:Eight-drug combination chemotherapy (MOPP and ABDV) and local radiotherapy for advanced Hodgkin's Disease. 6 21

A phase II study was conducted with three different combinations of cyclophosphamide, Oncovin (vincristine), methyl-CCNU, and bleomycin (COMB) in 106 patients with advanced bronchogenic carcinoma of all histologies. The response rates were 27.3% for COMB I (six of 22 patients), 18.2% for COMB II (eight of 44 patients), and 7.5% for vincristine, methyl-CCNU, and bleomycin (three of 40 patients). Complete responses were seen only in the small cell carcinoma group. Duration of remission and overall survival were of significance for the small cell group, whereas survival for the other histologic types comparing responders to nonresponders was of no statistical significance. Toxicity was significant and included nausea and vomiting, neuropathy, and myelosuppression. These drug combinations were disappointing and only in small cell carcinoma was meaningful antitumor activity seen.
Cancer Treat Rep
PMID:Combination chemotherapy with cyclophosphamide, vincristine, methyl-CCNU, and bleomycin in advanced bronchogenic carcinoma: experience with 106 patients. 6 95

A phase I-II study of cyclocytidine was conducted in 102 patients, 96 of whom had metastatic solid tumors and six of whom had acute leukemia. The drug was administered in 5- or 10-day courses of single daily iv or sc injections of 100-675 mg/m2 day. Two complete and six partial responses were observed in 64 solid tumor patients evaluable for response, 52 of whom had malignant melanoma or adenocarcinoma of gastrointestinal origin. The median duration of the responses was 6 months. An additional seven patients achieved stabilization of their disease for greater than or equal to 2 months. No responses occurred in six patients with acute leukemia. Side effects included nausea and vomiting, postural hypotension, and parotid pain, occurring in approximatley one third of patients receiving greater than 200 mg/m2/day. No myelosuppression was observed in six patients receiving 5-day courses of 100-200 mg/m2/day. Myelosuppressive toxicity became increasingly severe with doses greater than 200 mg/m2/day x 10, related at least in part to prior chemotherapy exposure including the nitrosoureas.
Cancer Treat Rep
PMID:Phase I-II evaluation of cyclocytidine. 6 28

Twenty-five patients with metastatic germ-cell tumors were treated with a combination of adriamycin, vincristine, and bleomycin. Fifteen patients (60%) had previously received radiation therapy, chemotherapy, or both. Twenty patients (80%) responded to treatment, with eight (32%) patients achieving a complete remission (CR) and 12 (48%) patients achieving a partial remission (PR). The median duration of response for the patients with PR was 4 months, whereas four patients with a CR remain alive without evidence of disease for greater than 3 years after the initiation of treatment. Responses were observed in all tumor categories and apparently were not influenced by prior therapy. Side effects included gastrointestinal toxicity, alopecia, neuropathy, skin changes, mucositis, and myelosuppression (more severe in previously treated patients). Though moderate success was demonstrated for this chemotherapy regimen, it does not appear as effective as more recent regimens including vinblastine and bleomycin.
Cancer Treat Rep 1977 Nov
PMID:Treatment of metastatic germ-cell tumors in men with adriamycin, vincristine, and bleomycin. 7 1

As bleomycin has up to now proved effective when used alone, the main thrust of current clinical investigations predominantly concerns its use in combination with other drugs. This has occurred along three broad patterns: 1) combination with vinca alkaloids which has been mainly in testicular carcinoma; 2) as part of multidrug regimens where bleomycin added for its lack of myelosuppression. This has occurred in the malignant lymphomas, lung cancer, and head and neck cancer; 3) in combination with radiotherapy which has taken place mostly in head and neck cervix cancer. To date, the combination of velban and bleomycin has had a major impact in improving the ability to induce complete remissions in advanced testicular carcinoma. Other drugs such as cis-platinum diaminedichloride and actinomycin D have been added and no definitive combination has been established. In the lymphomas the addition of bleomycin to the MOPP or CVP regimen has given higher complete response rates, but long-term survival data are still awaited.
Recent Results Cancer Res 1978
PMID:A review of the bleomycin experience in the United States. 8 99

A total of 77 patients with cancer of the head and neck area were treated with five different drug combination regimens. Five of the 77 patients had lymphoepithelioma; four had adenocystic carcinoma, and 68 had squamous-cell carcinoma of the head and neck (16 from the skin). Of these 77 patients, 16 had no previous treatment, five had surgery, 11 had radiotherapy, and 45 had surgery and radiotherapy. The first regimen consisted of a four-day Bleomycin infusion followed after a 24-hour rest, by cyclophosphamide (Cytoxan), Vincristine (Oncovin), methotrexate and 5-Fluorouracil (5-FU) (B-COMF). The next three regimens consisted of a four-day Bleomycin course, followed by either Cytoxan and methotrexate (B-CM), Cytoxan and 5-FU (B-CF) or Methotrexate and 5-FU (B-MF). The fifth regimen consisted of Bleomycin concomitant with Cytoxan, Methotrexate, and 5-FU (B-CMF). Of the 49 patients receiving B-COMF and B-CMF, 12 showed a complete response and 12 a partial response. Among the 28 patients receiving Bleomycin, followed by any one of the two drug regimens, only six showed a partial response. The severity of the thrombocytopenia, number of drugs, lymphoepithelioma histology and performance status of the patient influenced the rate of response. Drug toxicity consisted mostly in myelosuppression. The B-CMF combination is highly effective and can be used as an adjuvant to surgery and/or radiotherapy.
Cancer 1978 Oct
PMID:Combination chemotherapy of head and neck cancer. 8 14


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