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)

18 patients with metastatic or recurrent bronchogenic carcinoma and one patient with a squamous cell carcinoma of the trachea were treated with a combination of CCNU, hexamethylmelamine and methotrexate. Objective remissions were observed in 3/19 (16%): 1 complete, 1 partial (greater than 50%) and 1 incomplete (less than 50%). However, the patient with the complete response was the only drug death, on day 21. Remission duration in the other two patients was 3 and 9+ months respectively. One patient with oat cell carcinoma experienced no tumor progression for 5 months. This combination resulted in severe gastrointestinal toxicity in 5/19, severe thrombopenia in 12/19 and severe neutropenia in 6/19. We conclude that the combination as used here resulted in no increased clinical effectiveness and proved to be quite toxic.
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PMID:Combination chemotherapy with CCNU (NSC-79037),hexamethylmelamine (NSC-13875) and methotrexate (NSC-740) in advanced bronchogenic carcinoma. 81 58

Methyl-CCNU, a compound with marked antitumor activity against the solid Lewis lung tumor in mice, was submitted to a preclinical pharmacologic evaluation. The toxicity of a single iv infusion was tested in 37 beagle dogs and 21 rhesus monkeys. The minimum lethal dose (LD) in dogs was 14 mg/kg and five of six dogs died within 7-10 days after treatment from hematopoietic toxicity with neutropenia, lymphopenia, anemia, and concomitant sepsis. Metaplasia of the intestinal epithelium also occurred. Thrombocytopenia was not observed. Dogs treated with 9.27-1.56 mg/kg exhibited reversible neutropenia and lymphopenia but survived without severe morbidity or histopathologic lesions. In monkeys, interstitial nephritis was the treatment-limiting toxicity and three of six monkeys treated with 45 or 30 mg/kg died, became moribund, or exhibited severe renal histopathologic lesions. One monkey treated with 45 mg/kg had degeneration of the testes. Survivors exhibited reversible toxicity and no histopathologic lesions. Treatment with doses as low as 7.5 mg/kg caused reversible neutropenia, lymphopenia, and anemia. The largest nontoxic dose for a single iv infusion was 3.12 mg/kg (62.40 mg/m2) for the dog and 3.75 mg/kg (45 mg/m2) for the monkey. These and earlier observations showed that methyl-CCNU had approximately one third the toxicity of CCNU. Methyl-CCNU also did not cause the delayed hepatic toxicity which is characteristic of CCNU treatment in the dog.
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PMID:Methyl-CCNU: preclinical toxicologic evaluation of a single iv infusion in dogs and monkeys. 82 19

The development of a new multidrug chemotherapy regimen for primary brain tumors was based upon the cellular heterogeneity within individual tumors, the Goldie-Coldman and Price-Goldie-Hill hypotheses, and known agonistic effects of certain drug combinations and sequences. Eight drugs (vincristine [VCR], hydroxyurea, procarbazine, CCNU, cisplatin, cytosine arabinoside [Ara-C] high-dose methylprednisolone, and either cyclophosphamide or dacarbazine) were administered within 12 hours in an attempt to minimize myelosuppression. Courses were repeated at 2- to 4-week intervals. The regimen was devised to include lipid and water soluble drugs, polar and nonpolar agents, phase-specific and cell-cycle independent agents, and antineoplastics with different mechanisms of action. More than 330 courses of the regimen were administered to 107 children with brain tumors whose tumor had recurred or had been incompletely resected at diagnosis. Tumor response according to protocol-specified criteria and independent review was evaluable in 78% of the patients. After just two cycles of chemotherapy and within a 4- to 6-week interval, 50% had an objective tumor response including 15.5% who had a complete response (CR). Nephrotoxicity and high-frequency hearing losses were noted after three to five courses of therapy in approximately half of the patients. Transfusions with red cells or platelets and use of antibiotics for fever and neutropenia were required in 10% to 25% of patients. The regimen appears satisfactory for preradiation chemotherapy in newly diagnosed patients with residual tumor after surgery, but it must be compared with standard therapeutic approaches in prospective controlled trials before its relative value can be established.
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PMID:Eight drugs in one day chemotherapy for brain tumors: experience in 107 children and rationale for preradiation chemotherapy. 304 Sep 19

After stratification for extent of small cell lung cancer, 109 patients were randomized to receive cycles of chemotherapy with cyclophosphamide, doxorubicin, and VP-16-213 [CAVP16 (regimen I)] or to receive CAVP16 to maximum response (minimum of three courses) and then chemotherapy with CCNU, methotrexate, vincristine, and procarbazine (COMP) alternating with CAVP16 (regimen II). A group of patients who achieved complete remission were randomized to receive whole-brain irradiation or to have observation only. Of the 44 patients with limited disease, 28 (64%) achieved a complete remission and 11 (26%) achieved a partial remission. Of the 65 patients with extensive disease, 26 (40%) achieved a complete remission and 28 (46%) achieved a partial remission. There were no significant differences between the regimens in response or survival. The projected median survival times are 14 and 10 months for limited and extensive disease, respectively. Nearly 30% of patients with limited disease will be 2-year, disease-free survivors. Twenty-nine patients were randomized to receive cranial irradiation or observation only; none of the 15 irradiated patients developed cerebral metastases, but five of 14 randomized to observation relapsed in the brain (P = 0.02). One patient died with necropsy evidence of only intracranial disease. The principal hematologic toxic effect was leukopenia. There were 31 febrile episodes (21 infectious) during neutropenia and four toxic deaths. Nonhematologic toxicity was mild. Cranial irradiation in patients who achieve complete remission delays or reduces the incidence of CNS metastases. Although alternating chemotherapy is not beneficial, combination chemotherapy with CAVP16 alone is highly effective treatment modality for small cell.
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PMID:Combination chemotherapy for small cell carcinoma of the lung: continuous versus alternating non-cross-resistant combinations. 627 87

Forty patients with primary malignant brain tumor were treated by combination chemotherapy after prior treatment with surgery and radiotherapy. The chemotherapy schedule consisted of PCV: procarbazine per os, 100 mg/m2, during 14 consecutive days; CCNU, per os, 80 mg/m2 on day 1 and vincristine, intravenously, 1.4 mg/m2 on days 1 and 14. This protocol was planned to be repeated every 45 days for 6 courses. Median 5 courses (range, 2-6) of chemotherapy was administered to patients. The median relapse free (RFS) and overall survival (OS) rates were found to be 28 and 79+ months, respectively. According to univariate analysis, performance status (PS) of patients was an important prognostic factor on RFS and OS where extent of surgery was an additional significant determinant of OS. Multivariate analysis of pretreatment factors revealed the influence of sex, type of histopathology and PS on RFS and that of PS on OS rates (P < 0.05). The toxicity of this regimen was mild to moderate. The major toxicity noted was myelosuppression. Severe (grade III-IV) neutropenia and thrombocytopenia has been observed in 13 (7%) and 6 courses (3.5%), respectively. In general, PCV is well tolerated and the median RFS and OS times elucidated are comparable with particular trials utilizing combination chemotherapy and longer than using radiotherapy alone.
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PMID:Procarbazine, CCNU, vincristine combination in the treatment of brain tumors. 869 99

Between March 9, 1984 and January 29, 1992, 42 children with newly diagnosed symptomatic or previously diagnosed progressive low-grade gliomas received outpatient chemotherapy as their primary treatment. This study was a single arm, phase II trial designed to estimate the time to tumor progression and toxicity of this regimen. Procarbazine, 6-thioguanine, and dibromodulcitol were given before lomustine (CCNU) and vincristine was given 1 and 3 weeks after CCNU. Patients were treated for six treatment cycles or until the tumor progressed, whichever came first. Twenty-three patients had juvenile pilocytic astrocytomas, 11 had astrocytomas, one had oligodendroglioma, one had ganglioglioma, and six had radiographically diagnosed low-grade gliomas. The mean age of the patients was 5 years (median, 3 years). The median time to treatment failure was 132 weeks (95% confidence interval: 106, 186 weeks). Only eight patients have died the estimated 5-year survival rate is 78% (95% confidence interval, 60% 87%). There were two episodes of grade 4 neutropenia, and three episodes of grade 4 thrombocytopenia. This regimen was safe, able to be delivered in the outpatient setting, and produced prolonged periods of disease stabilization in children with low-grade gliomas.
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PMID:Treatment of pediatric low-grade gliomas with a nitrosourea-based multiagent chemotherapy regimen. 904 85

Forty-three dogs with lymphoma that had relapsed or had failed to achieve complete remission to previous chemotherapy were treated with lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea [CCNU]) at a dosage of 90-100 mg/m2 body surface area p.o. every 3 weeks. Durable complete or partial responses occurred in 11 dogs for a median of 86 days. The acutely dose-limiting toxicosis was neutropenia 7 days after administration, resulting in a recommended dosage of 90 mg/m2. Cumulative thrombocytopenia occurred in dogs receiving continued CCNU treatment, and a dose interval of 3 weeks may be too short for continued administration of this drug. Toxicoses evident as fever or central nervous system signs or renal damage were uncommon or rare. CCNU is effective in the treatment of relapsed lymphoma.
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PMID:Lomustine (CCNU) for the treatment of resistant lymphoma in dogs. 1049 18

The efficacy and toxicity of CCNU (1-[2-chloroethyl]3-cyclohexyl-1-nitrosourea) were evaluated in 23 dogs with measurable mast cell tumors (MCT). Twenty-two dogs had cutaneous MCT and 1 dog had an intranasal MCT Nineteen (83%) dogs had biopsy of their original mass performed and 4 (17%) had aspiration cytology of masses. Of the 19 tumors histologically graded, 1 (5%) neoplasm was classified as grade I, 10 (53%) were grade II, and the remaining 8 (42%) were grade III. Dogs were treated with CCNU at a dosage of 90 mg/m2 body surface area every 3 weeks. Response could be evaluated in 19 dogs. Eight of the 19 dogs (42%) had a measurable response to CCNU. One dog had a durable complete response for 440 days. Seven dogs (37%) had a partial response for a median and mean duration of 77 days and 109 days, respectively (range, 21-254 days). Treatment with CCNU resulted in stable disease in 6 dogs (32%) for a median and mean duration of 78 days and 122 days, respectively (range, 42-347 days). The acute dose-limiting toxicity was neutropenia 7 days after administration of CCNU. The median and mean neutrophil counts 7 days after CCNU were 1,452 cells/microL and 1,683 cells/microL, respectively (n = 17). Other toxicoses were uncommon. CCNU should be considered an active agent in the treatment of MCT in dogs.
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PMID:Treatment of canine mast cell tumors with CCNU (lomustine). 1058 63

We report the results of a non-randomized pilot study of an oral regimen comprising CCNU (lomustine; 25 or 50 mg/m2 on day 1), idarubicin (4-demethoxydaunorubicin) (10 mg/m2 on days 1-3) and dexamethasone (10 mg b.d. on days 1-4) in patients with relapsed or refractory myeloma. Treatment was given every 28 d for a maximum of six courses. Sixty patients were entered of whom 57 were evaluable. Overall response rate (partial or minor response) was 49% with 30% of patients achieving a partial response (50% tumour reduction). Response rates were higher in patients with untested relapse than in those with refractory disease (overall response rates 56% vs. 31%). The major toxicity was neutropenia and the regimen was otherwise well tolerated. The median survival from entry of all patients was 15 months, with 30% of patients alive at 2 years. This regimen represents a useful addition to available treatment options.
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PMID:CCNU (lomustine), idarubicin and dexamethasone (CIDEX): an effective oral regimen for the treatment of refractory or relapsed myeloma. 1109 Dec 28

A significant number of women with advanced breast cancer fail to respond to standard-dose chemotherapy. From the beginning of 1999, 17 women with HER2 positive advanced breast cancer received Herceptin as monotherapy or in combination with paclitaxel or other non-anthracyclines. Eight (47%) women previously received high-dose chemotherapy followed by haematopoiesis stem cell rescue. Three women received Herceptin alone, eleven Herceptin plus paclitaxel and three Herceptin and some of the other non-anthracyclines (CCNU, cisplatin and gemcitabine). In the group of patients who received Herceptin monotherapy, one has partial response (PR), one stable disease (SD) and in the third patient the disease progressed. Out of three patients who received Herceptin in combination with other non-anthracyclines, two have SD and one progressed. In the group of 11 women who received Herceptin + Taxol, 7 (64%) patients achieved PR, 2 (18%) SD, and 2 (18%) had disease progression. Grade 3-4 neutropenia has been observed in four (23%) women. Febrile neutropenia was observed in two cases and resolved completely when antibiotics were introduced. Other grade 3 toxicity that has been noted is peripheral neuropathy in three (18%) patients, diarrhoea in four (23%) and onycholysis in one (6%). Serial heart ultrasound showed no significant decline in left ventricular ejection fraction. According to our preliminary experience, Herceptin therapy showed promising results in women with metastatic breast cancer.
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PMID:Trastuzumab in the treatment of advanced breast cancer: single-center experience. 1152 30


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