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)

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.
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PMID:COMB (cyclophosphamide, oncovin, methyl-CCNU, and bleomycin): a four-drug combination in solid tumors. 5 Aug 70

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

Seventeen patients with advanced, previously treated Hodgkin's disease received therapy with a combination of streptozotocin 500 mg/m2/day i.v. days 1--5, CCNU 100 mg/m2 orally day 1, adriamycin 45 mg/m2 i.v. day 1, and bleomycin 15 mg/m2 i.m. days 1 and 8 at 28-day intervals (SCAB). The overall response rate was 59% with six patients (35%) achieving complete remission and four patients (24%) entering partial remissions. No maintenance therapy was given and the median duration of complete remission was 8+ months (range 2+-18+ months), while the median duration of partial remission was only 2 months (range 2-3 months). The median duration of survival from the start of therapy for the complete responders was 16+ months (range 5+-25+ months) while the median survival for the partial and nonresponders was only 5 months (range 2-13 and 3-11+ months, respectively). Toxicity was a major problem with this drug combination. Myelosuppression occurred regularly and was severe after 25% of courses. There were two deaths directly related to drug-induced myelosuppression. Other serious toxicities included bleomycin-induced pulmonary toxicity in three patients, with one death; renal tubular dysfunction secondary to streptozotocin in three patients; hepatic dysfunction in three patients and severe weight loss in three. SCAB has proven to be an active although toxic combination which is not cross-resistant to MOPP-type regimens. Alterations in drug dosages and scheduling are being evaluated in an effect to ameliorate toxicity and preserve efficacy.
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PMID:Combination chemotherapy of advanced previously treated Hodgkin's disease with streptozotocin, CCNU, adriamycin and bleomycin. 6 27

Chlorozotocin is a chloroethyl nitrosourea with a glucose carrier that has curative activity for the murine L1210 leukemia, but is nonmyelosuppressive in mice. To determine the mechanism for this unique property of reduced bone marrow toxicity, comparative studies were conducted with chlorozotocin and CCNU, a myelotoxic chloroethyl nitrosourea. Suspensions of L1210 leukemia and murine bone marrow cells were incubated for 2 h with 0.1 mM [(14)C]-chloroethyl chlorozotocin or CCNU. Chlorozotocin demonstrated a fourfold increased covalent binding of the chloroethyl group to L1210 nuclei when compared to equimolar CCNU. Chlorozotocin alkylation of L1210 cells resulted in the binding of 57 pmol of [(14)C]ethyl group/mg of DNA, which represented a 2.3-fold increased alkylation when compared to CCNU. In marked contrast, the binding of the chloroethyl group to bone marrow nuclei was equivalent for both drugs. In addition, chlorozotocin alkylation of murine bone marrow DNA, 45 pmol of [(14)C]ethyl group/mg of DNA, was equivalent to that of CCNU. The ratio of L1210:bone marrow DNA alkylation was 1.3 for chlorozotocin compared to 0.6 for CCNU. The intracellular carbamoylation of L1210 and bone marrow protein by CCNU was 400- to 600-fold greater than that produced by chlorozotocin. After a 2-h exposure to 0.1, 0.05, or 0.01 mM drug, both chlorozotocin and CCNU produced a reduction in the cloning efficiency of L1210 cells that was dose dependent. However, chlorozotocin was significantly more cytotoxic than CCNU at all three molar concentrations (P < 0.01). Chlorozotocin, 0.1 mM, reduced L1210 DNA synthesis to 1% of control by 48 h, in contrast to 16% with equimolar CCNU (P < 0.01). In mice bearing 10(5) L1210 cells, chlorozotocin produced its optimal antitumor activity (332% increased life span [ILS]) at doses of 48-64 mumol/kg, with >50% indefinite survivors. In contrast, CCNU at the same molar doses resulted in only a 191% ILS; a CCNU dose of 128 mumol/kg was required for comparable optimal L1210 antitumor activity, 413% ILS. On a molar basis, the dose of chlorozotocin that produced optimal in vivo L1210 antitumor activity was one-third to one-half that of CCNU. Chlorozotocin, unlike CCNU, produced no murine bone marrow toxicity at its optimal therapeutic dose. This unique combination of antitumor activity without myelosuppression can be correlated with the advantageous ratio of L1210:bone marrow in vitro DNA alkylation by chlorozotocin (1.3) as compared to equimolar CCNU (0.6).
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PMID:Chlorozotocin. Mechanism of reduced bone marrow toxicity in mice. 15 33

BCNU, CCNU, and methyl-CCNU have undergone extensive trial in multiple drug combinations for bronchogenic carcinoma. The addition of a nitrosourea appears to be an improvement over cyclophosphamide used alone in oat cell carcinoma and over the two drug combination of cyclophosphamide and methotrexate in both adenocarcinoma of the lung and oat cell disease. Encouraging response rates have been seen in squamous lung cancer with multiple-drug combinations of a nitrosourea, an alkylating agent, vincristine, and bleomycin with or without adriamycin. The nitrosoureas have been easily incorporated, at reduced doses, into multiple-drug regimens with cumulative myelosuppression seen only when the interval between nitrosourea doses is less than 6 weeks. Conclusions about the ultimate role of these compounds in lunb cancer treatment must await (a) comparative trials of combinations with and without a nitrosourea, and (b) further exploration of new approaches to increase their therapeutic index.
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PMID:Nitrosourea combinations in lung cancer. 18 65

The MACC (methotrexate, adriamycin, cyclophosphamide, CCNU) regimen was administered to 43 patients with advanced epidermoid and adenocarcinoma of the lung. Only 5 patients (12%), all of whom were ambulatory responded with partial remissions. Median time to progression for the 5 responders was 20 weeks from start of treatment. Median survival was 15.5 weeks for patients with epidermoid cancer and 14.4 weeks for those with adenocarcinoma. Hematologic toxicity was severe, with 2 treatment-related deaths during profound myelosuppression. White blood counts below 2000/microliter were reported in 47%, and below 1,000/microliter in 26%. Since the activity of this regimen, given as it was in full doses, is not superior to that achieved with standard doses of single agents which are less toxic, further employment of the MACC regimen is not recommended, either for advanced disease or as a surgical adjuvant.
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PMID:MACC chemotherapy for adenocarcinoma and epidermoid carcinoma of the lung: low response rate in a Cooperative Group Study. Eastern Cooperative Oncology Group. 47 98

Synthetic studies on new antitumor drugs in Japan are mainly oriented toward analogs of known active structures. In the nitrosourea area ACNU, a pyrimidine analog of CCNU, is currently under clinical investigation and has myelosuppression as a side effect Nitrosoureas with a sugar moiety are of great interest and two compounds called GANU and MCNU are now ready for phase I study in Japan. Among new alkylating agents are included a series of bis-methanesulfonate of aminoglycols, an analog of cyclophosphamide called 4-hydroperoxy-cyclophosphamide, and aziridine derivatives which include the now commercially available carbazilquinone. In the antimetabolite field cyclocytidine is an analog of arabinosyl cytosine which has been extensively studied. A newer analog called N4-behenoyl-cytosine arabinoside is now being studied experimentally. In the fluorinated pyrimidine area Ftorafur has been extensively studied and a new compound FD-1 is of interest.
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PMID:Synthetic analogs of antitumor drugs under development in Japan. 70 11

The recently synthesized nitrosourea, N-[N'-chloro-2-ethyl-N'-nitrosocarbamoyl]-S-methyl cysteamine sulfoxide (Perrimustine), is water soluble and has a high alkylating activity, similar to that of the widely used nitrsoureas BCNU and CCNU, and a low carbamoylating activity. Preclinical studies with a broad spectrum of murine tumors indicate that this new compound may be clinically useful. The maximally efficient dose range (MEDR) in L1210 bearing mice was 45 mg/m2 (subcurative dose) to 67 mg/m2 (subtoxic dose). The present phase I trial used an intrapatient escalation schedule, so that each patient entering the study received a potentially active dose. The first dose injected was 1:100 of the MEDR suboptimal dose to check for anaphylactic sensitivity. Patients were then given increasing doses at increasing time intervals until toxicity was observed. The highest dose was given on day 150-230. The main toxic effect was myelosuppression [five out of the 24 patients evaluated: one grade 4 thrombocytopenia, two grade 3 thrombocytopenia; anemia and leucopenia were milder (grade 1 to 2 on OMS scale)]. Of the 19 patients evaluated for clinical response, one showed response after the 45 mg/m2 dose (disappearance of the cerebral metastasis with persistence of hepatic localizations in a patient with melanoma) and the disease was stabilized in two cases (a pleural mesothelioma and a renal carcinoma with lung metastases) after 26 and 37 weeks, with total cumulative doses per m2 of 232 and 196 mg, respectively.
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PMID:Phase I trial of Perrimustine, a new cysteamine (2-chloroethyl) nitrosourea: an intrapatient escalation scheme. 152 2

Thirty-one patients affected by recurrent Hodgkin's disease have been treated with an oral combination chemotherapy including lomustine (CCNU 90 mg/sqm, on day 1), melphalan (Alkeran, 7.5 mg/sqm on days 1-5), etoposide (VP-16, 100 mg/sqm on days 6-10) and prednisone (40 mg/sqm on days 1-10). MOPP and ABVD regimens administered sequentially or in alternating fashion had been employed as first choice treatment. The majority of patients had extranodal (80%) and a progressive disease resistant to previous chemotherapy (80%). Complete and partial remission were induced in 8 (26%) and 5 patients (16%), respectively, with an overall response rate of 42%. Median duration of complete remission was 10 months. Patients who did not respond to previous chemotherapies had a significantly lower complete response rate (16%). Myelosuppression was the most frequent complication, with one patient dying of a thrombocytopenic hemorrhage. The oral administration of drugs allowed good patients', compliance with treatment. CAVP is an effective regimen in the management of patients with refractory Hodgkin's disease and the results obtained are comparable with other third-line chemotherapies.
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PMID:Third-line chemotherapy with CAVP (CCNU, melphalan, etoposide and prednisone) in refractory Hodgkin's disease. 251 Oct 96

Ninety-two nonsmall cell lung cancer (NSCLC) patients were treated with a combination chemotherapy containing methotrexate, adriamycin, cyclophosphamide and CCNU (MACC). The regimen was administered in the dose and schedule originally reported. Median survival for all patients was 32 weeks. Only 6 patients demonstrated an objective response with a median survival rate of 51 weeks. The remaining 70 evaluable patients were nonresponders. These latter patients had a survival probability reduced to 29 weeks. Median time to progression for the whole group was 17 weeks. Partial responses were seen in 3 squamous, 1 large cell carcinoma and 1 adenocarcinoma. One patient with bronchiolo-alveolar carcinoma had complete disease regression and is still alive 136 weeks after starting treatment. Toxicity was significant with 2 treatment-related deaths. The major toxic effects consisted of myelosuppression, nausea, vomiting, and stomatitis. Alopecia was nearly universal; a mild cardiac, renal, or hepatic toxicity was relatively infrequent. Polychemotherapy with MACC regimen may benefit a few selected patients with NSCLC, but its overall antitumor efficacy appears to be very limited.
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PMID:Combination chemotherapy with methotrexate, adriamycin, cyclophosphamide and CCNU (MACC) for nonsmall cell lung cancer. 4-year experience with 92 patients. 254 37


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