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)

Carboplatin is a 'second-generation' platinum compound advocated for use in the treatment of patients with ovarian cancer and it has also shown promise in small cell lung cancer, squamous cell carcinomas of the head and neck, and seminomas. Overall, it would appear to have a similar qualitative spectrum of activity to cisplatin. There have been few comparative trials with carboplatin, either alone or in combination with other chemotherapeutic agents, but the limited data suggest comparable efficacy with cisplatin in ovarian cancer. Importantly, the toxicity profile of carboplatin is markedly different from that of cisplatin, with nephrotoxicity, neurotoxicity and ototoxicity occurring only infrequently with carboplatin. As with cisplatin, nausea and vomiting occur in many patients after carboplatin administration, but symptoms are usually delayed for several hours and are mild to moderate in severity - dose-limiting nausea and vomiting are infrequent with carboplatin. The dose-limiting toxicity of carboplatin is myelosuppression, with severe thrombocytopenia and less often leucopenia, which may be more severe in older patients or in those with renal impairment or those who have had previous chemotherapy. Thus, preliminary data suggest that carboplatin is a therapeutically equivalent alternative to cisplatin, but with a differing toxicity profile that should offer advantages over cisplatin in many patients.
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PMID:Carboplatin. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of cancer. 264 54

Six previously untreated poor prognosis patients and eight previously treated patients with small cell lung cancer (SCC) were treated with 1,2,4-triglycidylurazol (TGU, NSC-332488) 800 and 650 mg/m2 every 4 weeks, respectively. No responses were observed. The survival time of the previously untreated patients was short, a median of 7 weeks (range 5-10 weeks). Myelosuppression was severe and prolonged with white blood count, WHO grade 3-4, in four previously untreated patients and in two previously patients, and with platelets, WHO grade 3-4, in both four previously untreated and in four previously treated patients. Gastrointestinal toxicity was mild to moderate. It is concluded that TGU is inactive in SCC.
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PMID:Phase II study of 1,2,4-triglycidylurazol (TGU) in previously untreated and treated patients with small cell lung cancer. 282 24

Sixty-five patients with small cell lung cancer were treated with VP16, vincristine, cyclophosphamide, and doxorubicin (VOCA) intravenously at three-week intervals. Patients with limited disease received four cycles with responders receiving radiation to the primary site and prophylactic cranial irradiation. Patients with extensive disease received chemotherapy only. Of 59 patients evaluable for chemotherapy response, eight (14%) achieved complete remission and 30 (51%) partial remission. Major side-effects included myelosuppression, alopecia, nausea, and vomiting. Reinduction with VOCA at relapse yielded objective or subjective response in four of seven patients. This regimen is active in small cell lung cancer and was well tolerated by patients. Reinduction of response was possible in a small number of patients retreated and may provide useful palliation for those who relapse when treatment is discontinued.
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PMID:Chemotherapy for small cell lung cancer: induction and reinduction with VOCA. 282 61

The soft, gelatin capsule of VP-16-213 (etoposide) was given orally and evaluated in a Phase II study of 56 patients with histologically confirmed small cell lung cancer. The drug was given in a dose of 200 mg/body/day orally for 5 consecutive days, and the courses were repeated every 3 to 4 weeks depending upon the individual patient recovery from myelosuppression. An overall objective response was obtained in 17 patients (30%), five previously treated (23%) and 12 untreated (35%). The median days for response after the start of treatment was 14 d (range, 5 to 64), and the median duration of response was 62 days (range, 28 to 278). The dose-limiting factor was leukopenia, while thrombocytopenia was also experienced. Gastrointestinal reactions to toxicity and alopecia were also observed, but they were not overwhelming. The study demonstrated that the VP-16-213 soft gelatin capsule given orally is effective against small cell lung cancer without clinical cross-resistance to other cytotoxic agents. Its usefulness in combination chemotherapy is thus suggested.
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PMID:Phase II study of oral VP-16-213 in small cell lung cancer. 282 17

Sixteen patients with lung cancer or mesothelioma have been treated with escalating doses of carboplatin. Five patients (10 courses) were given 800 mg/m2, four patients (five courses) 1200 mg/m2 and seven patients (eight courses) 1600 mg/m2. Myelosuppression was the major toxicity encountered. The median duration of grade 4 neutropenia ranged from 1 day (800 mg/m2) to 11 days (1600 mg/m2) and the median duration of grade 4 thrombocytopenia ranged from 1 day (800 mg/m2) to 7 days (1600 mg/m2). The median fall in haemoglobin (Hb) ranged from 2.2 g/l (800 mg/m2) to 3.6 g/l (1600 mg/m2). Nephrotoxicity was encountered at all dosages and was in part, though not entirely, dose related. 2/9 patients receiving 800 mg/m2 and 4/6 of the patients receiving 1600 mg/m2 had a fall in glomerular filtration rate (GFR) greater than 25% but less than 50%. 800 mg/m2 of carboplatin was well tolerated, the performance status in 9/10 (90%) courses being 0-1 (ECOG scale). At 1600 mg/m2 in 6/8 (75%) courses the performance status was 2-4. There was one treatment-related death from neutropenia at this dose level. The severity of nausea and vomiting was not dose related but other toxicities including diarrhoea, alopecia, mild neuropathy and ototoxicity and possible CNS toxicity occurred at doses of 1200 mg/m2 and over. 5/7 patients with small cell lung cancer achieved a complete or partial response to treatment.
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PMID:High dose carboplatin in the treatment of lung cancer and mesothelioma: a phase I dose escalation study. 282 9

Carboplatin (CBDCA; cis-diammine-1, 1-cyclobutane dicarboxylate platinum II), a new platinum analogue, was administered to 18 patients with small cell lung cancer (SCLC) at a dose of 300-450 mg/m2 intravenously every four weeks, in a phase II study. All patients could be evaluated to assess response and 17 for toxicity. The overall response rate was 28% (5/18), including one complete response. Of eight patients previously untreated, four (50%) showed a response, including one complete response. The response rate in patients with no previous cisplatin-treatment was 50% (5/10). Response durations in five responders were 2, 3, greater than 4, greater than 10 and 11 months. Toxicity was primarily hematologic, with thrombocytopenia being dose-limiting. Thrombocytopenia (less than 75,000/mm3) was observed in 12 patients (71%), six requiring platelet transfusion. Leukopenia (less than 3,000/mm3) was observed in 11 patients (65%). There were no episodes of serious infection or bleeding, however. Myelosuppression was more severe in heavily pretreated patients than in patients previously untreated. Dose reductions were required following multiple treatments for cumulative myelotoxicity. Mild to moderate nausea and vomiting occurred in seven patients (44%). Nephrotoxicity and ototoxicity were not observed. Carboplatin was demonstrated to be an active agent against SCLC. Further investigation into dose and schedule of CBDCA in combination chemotherapy is warranted.
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PMID:Phase II study of carboplatin in small cell lung cancer. 283 35

Sixty-one patients affected by small cell lung cancer (SCLC) entered in the study. Eighteen had limited disease and 43 extensive disease. Treatment consisted of: induction chemotherapy with 3 courses of CAV (cyclophosphamide, adriamycin, vincristine) in limited disease patients or 2 courses of CAV plus 2 courses of DDP-VP16 (cisplatin, etoposide) in extensive disease patients, followed by chest radiotherapy and CNS prophylaxis in responsive patients. Subsequently, responders and stable patients received maintenance chemotherapy by the alternation of cycles of CAV, DDP-VP16 and C'MP (CCNU, methotrexate, procarbazine), which lasted 1 year or until relapse. Four of 17 limited disease patients (23%) obtained a CR and 11 (65%) a PR; their median survival was 11 months (range, 2+-36+). One of the 7 extensive disease patients (3%) achieved a CR and 19 (51%) a PR; their median survival was 6 months (range, 1-22). Median duration of response was 12 months for CR and 5 months for PR. Responders (CR and PR) survived 11.5 months versus 3.5 months for failures (P less than 0.05); 3/61 (5%) showed long-term survival, in the absence of disease. The overall median survival was 7 months (range, 1-36+). The main toxic effects were myelosuppression and vomiting (WHO grade 3). From our results, this program does not offer further substantial gains in patients with SCLC.
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PMID:Results of a combined chemo-radiotherapeutic program in 61 patients affected by small cell lung cancer. 283 45

Forty-four evaluable, previously untreated patients with small cell lung cancer were treated with two courses of induction chemotherapy consisting of POCC. Subsequently, all limited-disease patients and extensive-disease patients in CR received 4,000 to 5,000 cGy irradiation over 4 to 5 weeks (or the equivalent) to the primary tumor, mediastinum and supraclavicular areas and 3,000 cGy prophylactic cranial irradiation during 2 weeks. All patients received maintenance chemotherapy for a full year after CR or until disease progression. Eleven continued POCC while 33 received vinblastine, cyclophosphamide, and either adriamycin or methotrexate on an alternating schedule (VCMA). For the 20 limited-disease patients, the CR rate was 70% and the PR rate was 20%. Median survival was 22 months, local control was 62%, 2-year DFS was 35% and 3-year DFS was 20%. Of the 24 extensive-disease patients only 21% achieved CR and 54% achieved PR. Median survival was only 8 months and there were no disease-free survivors at 2 years. Toxicity was moderate with nausea and vomiting in all patients, and there were two deaths from myelosuppression in the group that received POCC maintenance therapy; there were no drug-related deaths in the VCMA group. Since these results are similar to those obtained with simpler regimes, we cannot recommend our regimen for the treatment of small cell lung cancer. The optimal treatment for this disease has yet to be elucidated.
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PMID:Chemotherapy induction, consolidation radiotherapy and maintenance alternating chemotherapy in small cell carcinoma of the lung. 284 98

Thirty-four previously untreated patients with extensive small cell lung cancer were treated with a combination of carboplatin 300 mg m-2 i.v. on day 1 and etoposide 100 mg m-2 i.v. on days 1, 2 and 3 every 28 days. Thirty-two patients were assessable for response. Eighteen patients (56%) achieved an objective response (95% confidence limits 38%-73%). Five (16%) had a complete response and 13 (41.0%) had a partial response. The median time to response was 7.8 weeks and the median duration of response was 23.1 weeks (range 6.2 to 54 weeks). The median survival of all 34 extensive disease patients was 34.7 weeks (range 1.3-59.3 weeks). Myelosuppression (leukopenia) was the main toxicity. There was one early death that may have been treatment-related. Biochemical renal dysfunction was noted in two patients. Paresthesiae and tinnitus/hearing loss were described by three and two patients respectively. Serious gastrointestinal toxicity was infrequent. This and other studies have shown this combination to be active and well tolerated in small cell lung cancer; however, it is not yet clear if it is as efficacious as the more commonly used VP-16-cisplatin regimen.
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PMID:VP-16 and carboplatin in previously untreated patients with extensive small cell lung cancer: a study of the National Cancer Institute of Canada Clinical Trials Group. 284 76

Carboplatin, a cisplatin analog without significant clinical nephrotoxicity, has been evaluated in the treatment of 56 patients with small cell lung carcinoma at a dose of 300-400 mg/m2 iv monthly in a phase II study. Twenty-three patients (41%) achieved a response, including five (9%) complete remissions. Of 30 previously untreated patients, 18 (60%) achieved a response, including three (10%) complete remissions. Median response duration was 4.5 months (range, 2-9). No nephrotoxicity was seen and hydration was not required. Nausea or vomiting occurred in only 24 patients (43%) and was rarely severe. Myelosuppression was dose-limiting: 20 patients (36%) developed leukopenia and eight (14%) developed thrombocytopenia, but leukopenic infections occurred in only three patients. Carboplatin is a very active new agent in the treatment of small cell lung cancer, with less toxicity and better tolerance than cisplatin. It merits further investigation in combination chemotherapy and against non-small cell lung cancer.
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PMID:Carboplatin: a very active new cisplatin analog in the treatment of small cell lung cancer. 298 20


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