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)

Forty-six patients with previously untreated, advanced ovarian cancer received carboplatin (JM8, CBDCA) and chlorambucil (CLB) to assess the efficacy and toxicity of this combination. Carboplatin 300 mg m-2 was given on day 1 with CLB 10 mg daily for 7, 10 or 14 days; 6 treatment courses were given at 4-6 weekly intervals in the absence of disease progression. Tumour response was assessed, where possible, by restaging laparotomy after 6 treatment cycles. Five complete and 16 partial remission were seen in 37 evaluable patients giving an overall response rate of 57%. The median survival of all patients was 15 months. The major toxicity was myelosuppression. Nausea and vomiting were generally minor (WHO, grades I or II) and most courses were given on an outpatient basis. Leucopenia was the major factor causing treatment delays, particularly with the 10 and 14 day CLB regimens. Thrombocytopenia was minimal in the early chemotherapy cycles but the data suggest that cumulative toxicity may occur. This combination may provide a satisfactory degree of efficacy with less toxicity than cisplatin-based regimens.
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PMID:A pilot study of carboplatin (JM8, CBDCA) and chlorambucil in combination for advanced ovarian cancer. 306 98

Carboplatin was evaluated in a Phase I and pharmacokinetic study at the Royal Marsden Hospital between April 1981 and November 1981. Sixty patients were entered of whom 16 had impaired renal function. No evidence of ototoxicity or nephrotoxicity was found. Nausea and vomiting were much reduced compared to cisplatin. The dose limiting toxicity was delayed myelosuppression with thrombocytopenia being more severe than leucopenia. A number of clinical responses were seen, particularly in patients with ovarian carcinoma. Pharmacokinetic studies suggested that the dose of JM8 should be adjusted according to the glomerular filtration rate.
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PMID:Phase I studies with carboplatin at the Royal Marsden Hospital. 391 Feb 22

cis-Diammine-1,1-cyclobutane dicarboxylate platinum II (CBDCA, JM8), an analogue of cisplatin showing reduced toxicity in preclinical studies, was evaluated in 60 patients. Doses were given initially every 3 weeks and escalated from 20 to 520 mg/m2. Following this, doses were given every 4 weeks and escalated from 300 to 500 mg/m2. The dose-limiting toxicity, thrombocytopoenia, occurred in four-fifths of patients treated at 520 mg/m2, with the nadir occurring 3 weeks after treatment. Leucopoenia and anaemia also occurred but were less severe. Vomiting occurred in all patients receiving over 120 mg/m2 but seldom persisted beyond 24 h. Serial measurements of 51Cr-EDTA clearances, urinary N-acetylglucosaminidase, urinary leucine aminopeptidase, and beta 2-microglobulin did not reveal significant evidence of nephrotoxicity. Detriment to the audiogram has not been seen in the first 13 patients studied. Pharmacological studies showed that most of the dose of platinum was excreted in the urine, and that impairment of renal function may be associated with drug retention and an increased risk of myelosuppression. The previous therapy and age of the patient also affected the tolerance of the drug. Clinical responses were seen in patients with ovarian carcinoma receiving greater than 120 mg/m2. A further dose escalation was performed on a 4-week schedule in patients under 65 with good renal function. The maximum dose it was possible to administer repeatedly without incurring myelosuppression was in the range 400-500 mg/m2. JM8 is not significantly nephrotoxic and is less emetic than cisplatin. It has antitumour activity in man and deserves wider evaluation, along with the other analogues under study in various centres, as an alternative to cisplatin.
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PMID:Early clinical studies with cis-diammine-1,1-cyclobutane dicarboxylate platinum II. 676 Oct 10