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Biomedical subjects

A H Calvert

Publications and source records attributed to A H Calvert.

At least 145 records · Page 8Linked to original sources
PubMed1983

Studies on the pharmacokinetics of chlorambucil and prednimustine in man.

1 Chlorambucil (10 mg) and prednimustine (20 mg), the prednisolone ester of chlorambucil, were administered orally on separate occasions to six patients. 2 Chlorambucil was rapidly absorbed such that the parent compound was observed in the plasma 30 min after administration. 3 A preliminary comparison of chlorambucil levels following oral and intravenous administration, and after repeat oral dosage indicated that chlorambucil was well (greater than 70%) and consistently absorbed. 4 Following prednimustine no parent drug or alkylating metabolites (chlorambucil or phenyl acetic mustard) could be detected in the plasma. 5 In studies with intravenously administered chlorambucil plasma levels of the parent drug were described by a two-compartment open model with first-order kinetics. Significant levels of the cytotoxic metabolite phenyl acetic mustard were detected. 6 It is concluded that: a. the bioavailability of orally administered prednimustine is much lower than that of chlorambucil. Thus the use of prednimustine in routine combination therapy is not recommended. b. due to the lower therapeutic index of phenyl acetic mustard in experimental systems, the production of this metabolite in man may be disadvantageous. Thus research aimed at producing chlorambucil analogues, which cannot be metabolised, seems justified.

Administration, Oral↗
PubMed1983

Phase II study of JM8, a new platinum analog, in advanced ovarian carcinoma.

A phase II study of JM8, an analog of cisplatin, has been carried out in 36 patients with advanced ovarian carcinoma. Thirty-three of these patients had recurrent carcinoma and had been heavily pretreated, either with cytotoxic drugs alone (28 patients) or with cytotoxic drugs and radiotherapy (five patients). All patients had previously received cisplatin, either alone or as part of a combination, and some of them had previously been treated with as many as four different chemotherapy regimens. In addition, three patients with stage III ovarian carcinoma were treated with JM8 as first-line therapy. Twenty-eight of the 33 pretreated patients were evaluable for response, and five partial and two complete remissions were achieved. Of the seven responders, four had previously been shown to be completely resistant to cisplatin, and a fifth had initially responded to, but subsequently relapsed, while receiving cisplatin. Renal, aural, and neurotoxic effects were less than would have been expected with cisplatin, but hematologic toxic effects were common, with a wbc count of less than 2000 X 10(9)/L recorded in six patients, and a platelet count of less than 50,000 X 10(9)/L recorded in eight patients.

Antineoplastic Agents↗
PubMed1982

Early clinical studies with cis-diammine-1,1-cyclobutane dicarboxylate platinum II.

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.

Adult↗
PubMed1981

Methotrexate with thymidine, inosine, and allopurinol rescue: a phase I clinical study.

A phase I clinical study of a combination of thymidine (TdR), inosine (IR), and allopurinol used as rescue from 24-hour infusions of methotrexate (MTX) was undertaken following animal studies that had shown a better preservation of antitumor activity with this system than with folinic acid. TdR and IR were given in the dose ratio 5:1 by weight throughout. Rescue from MTX, 400 mg/m2, could be achieved with a TdR dose in the combination of 1 g/m2/24 hours. This same rescue was also effective when the MTX dose was increased to 800 mg/m2, but only partly effective at an MTX dose of 1.5 g/m2. It was not necessary to raise the levels of circulating nucleosides significantly above normal to achieve rescue. MTX-related skin lesions occurred more frequently than might be expected with the MTX dose used.

Adult↗
PubMed1978

Improved results in combination chemotherapy of head and neck cancer using a kinetically-based approach: a randomised study with and without adriamycin.

One hundred and seventeen patients with advanced squamous cell carcinoma of the head and neck were randomised between two combination schedules, one with and the other without adramycin. Responses (more than 50% tumor regression) were 67% overall with 63% responding to the combination without adriamycin and 82% responding to the schedule containing it. The increase in response rate seen with the addition of adriamycin is not statistically significant. Prior radiotherapy reduced the likelihood of response to chemotherapy.

Antineoplastic Agents↗
PubMed1977

Some observations on the human pharmacology of methotrexate.

Plasma and urinary levels of methotrexate (MTX) have been measured enzymatically in 18 patients receiving doses of 5-1250 mg. When tritium-labeled MTX was administered, plasma levels measured by radioisotope counting were significantly higher than those measured enzymatically, the difference being accounted for by the presence of tritium label in plasma water as a result of drug metabolism. Renal clearance of MTX correlated well with glomerular filtration rate (GFR) and was consistently lower than the GFR, suggesting tubular reabsorption of the drug at the rate of urine flow studied. Plasma clearance measured by an infusion method was consistently greater than renal clearance, suggesting drug metabolism. Biliary MTX levels have been measured in three patients and are very much higher than plasma levels, suggesting a quantitatively important biliary recirculation of the drug. Plasma levels of MTX measured after 24 hours were not significantly different following iv or im administration, but were higher if an infusion was used.

Bile↗
PubMed1975

Kinetically-based multiple drug treatment for advanced head and neck cancer.

A multiple drug regimen was given to 36 patients with advanced carcinomas of the head and neck. In 19 of the 24 patients who were assessable the tumour regressed more than 50%; in one it regressed by 25%; and in four it did not respond at all. Multiple drug chemotherapy should be given much earlier in the course of these cancers, preferably as an adjuvant to surgery or radiotherapy.

Antineoplastic Agents↗
PubMedDate not supplied

A randomized combination chemotherapy trial, with and without adriamycin, in squamous cell carcinoma of the head and neck.

One hundred seventeen patients with advanced squamous cell carcinoma of the head and neck were treated and placed randomly between two combination protocols, one with adriamycin and the other without. Responses (more than 50% tumor regression) were 67% overall with 63% responding to the combination without adriamycin and 82% responding to the protocol containing it. The increase in the response rate seen with the addition of adriamycin was not statistically significant. The degree of response to chemotherapy was reduced by prior radiotherapy.

Bleomycin↗