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Biomedical subjects

R M Fox

Publications and source records attributed to R M Fox.

At least 145 records · Page 8Linked to original sources
PubMed1981

Allopurinol modulation of fluorouracil toxicity.

Considerable interest has developed in the modulation of fluorouracil activity by nucleosides. The toxicity of fluorouracil in mice is known to be reduced by concurrent administration of allopurinol, presumably because biochemical pathways activating fluorouracil in normal tissues are blocked. We have given allopurinol (300 mg t.d.s. PO) concurrently with continuous infusions of fluorouracil (2.0--2.25 g/m2/day X 5) to 34 patients with colorectal cancer and 11 patients with various adenocarcinomas. There were 41 patients assessable for toxicity. Stomatitis was the predominant dose-limiting toxicity (22% grade 1, 19% grade 2, and 27% grade 3 toxicity). Neutropenia (Less Than 1,000/mu l) occurred in 17% patients. Among 26 colorectal cancer patients assessable for response there was a 15.4% response rate. We conclude that allopurinol modulates fluorouracil toxicity in man, allowing a two-fold increase in dose. However, at least in colorectal cancer no greater frequency of tumour response is seen than with lower doses of fluorouracil given by standard schedules of administration without allopurinol.

Allopurinol↗
PubMed1981

The treatment of metastatic breast cancer with aminoglutethimide.

Thirty-eight patients with advanced breast cancer, resistant to prior endocrine therapy and in most cases prior chemotherapy, were treated with aminoglutethimide, 250 mg qds. Seven of 30 evaluable patients (23%) responded. Six have subsequently relapsed with a mean duration of response of 17 weeks, while one continues to respond after 50 weeks of therapy. Six additional patients (20%) had stable disease during aminoglutethimide therapy (mean duration of 16 weeks). Three of the seven responders had shown a partial response, two had stable disease and two had progressive disease on prior endocrine therapy (including tamoxifen); six of the seven patients responding to aminoglutethimide had received prior combination chemotherapy, to which all had responded. Aminoglutethimide was generally well tolerated, although three patients withdrew from treatment within the first two weeks because of intolerable drowsiness. Aminoglutethimide offers a useful alternative to surgical adrenalectomy for women with advanced breast cancer responsive to previous endocrine and cytotoxic chemotherapy.

Adult↗
PubMed1981

Ecto-adenosine triphosphatase deficiency in cultured human T and null leukemic lymphocytes. A biochemical basis for thymidine sensitivity.

Cultured leukemic T and null lymphocytes are highly sensitive to growth inhibition by thymidine, as well as the other deoxynucleosides, deoxyguanosine and deoxyadenosine. By contrast, Epstein-Barr virus-transformed B lymphocytes are relatively resistant to deoxynucleosides. Growth inhibition is associated with the development of high deoxyribotriphosphate pools after exposure to the respective deoxynucleotides. We show that malignant T and null lymphocytes are deficient in ecto-ATPase activity. We show this cell surface enzyme to be of broad specificity, capable of degrading both ribotriphosphates and deoxyribotriphosphates. High levels of this ecto-enzyme are found in deoxynucleoside-resistant, Epstein-Barr virus-transformed B lymphocytes. Ecto-ATPase deficiency may represent a mechanism for increased sensitivity to deoxynucleoside growth inhibition.

Adenosine Triphosphatases↗
PubMed1981

G1-phase arrest of cultured human leukemic T-cells induced by deoxyadenosine.

Cultured human T-cell leukemia lymphocytes have enhanced sensitivity to growth inhibition by deoxyadenosine. We have used flow cytometry to investigate the mechanism of deoxyadenosine toxicity in cultured T-leukemic cells. Comparative studies on deoxyadenosine-resistant Epstein-Barr virus-transformed B-lymphocyte cell lines were also performed. After exposure of T-cells to low concentrations of deoxyadenosine (3 microM), in the presence of an adenosine deaminase inhibitor (erythro-9-[3-(2-hydroxynonyl)]adenosine), accumulation of cells of cells with a G1 DNA content was demonstrated. In contrast, B-cell lines showed a similar degree of growth inhibition after exposure to 200 to 400 microM deoxyadenosine but were blocked in S phase. The T-cell G1 block was associated with a rise in the deoxyadenosine triphosphate pool, and both these phenomena were prevented by the addition of deoxycytidine. The biochemical mechanism of this G1 block induced by deoxyadenosine in T-cells is not understood.

Adenosine Kinase↗
PubMed1981

Methotrexate treatment of advanced head and neck cancers: a dose response evaluation.

Fifty-eight patients with advanced squamous cell cancer of the head and neck have been randomized on a study comparing three different weekly methotrexate (MTX) dose levels followed at 24 hours by standardized folinic acid rescue. Eighteen patients received MTX 5 g/m2, 24 patients received 500 mg/m2, and 16 patients received 50 mg/m2. The initial response rate according to treatment were 50%, 21% and 31%, respectively. Six patients crossed from low- to medium-dose MTX after failing to respond (four) or relapsing, and one in each group had a tumor response. Eleven patients crossed over from initial medium-dose to high-dose MTX after failing to respond (ten) or relapsing, and one in each group had a tumor response. The median time to maximum response was 3.5 weeks. There were only two complete responders, and one is disease free more than 19 months after starting treatment and more than 15 months after stopping treatment. The high-dose MTX treatment was significantly more toxic than lower doses, and there were four drug-related deaths (three in the high-dose group). The preliminary results of this study support the notion of a dose-response relationship to MTX in advanced squamous cell cancer of the head and neck.

Adolescent↗
PubMed1981

Cyclical combination chemotherapeutic regimen in adult soft tissue sarcoma.

A cyclical combination chemotherapeutic regimen of Adriamycin and cyclophosphamide alternating with actinomycin D and DTIC was administered to 20 evaluable patients with metastatic soft tissue sarcoma. Responses included four (20%) partial remissions and five (25%) patients with stable disease. There was a significant prolongation of survival for responding patients (median 42.5+ weeks) compared to patients with progressive disease (median 17.5 weeks). Principal toxicity was nausea and vomiting particularly with the actinomycin D/DTIC combination and four patients found this so intolerable they withdrew from study. These results are inferior to those reported for Adriamycin alone and other combinations. Further evaluation of the concept of sequential non-cross-resistant combinations would only seem appropriate if newer more active agents are identified and each combination is administered for a set duration before crossing over to the alternative regimen.

Adult↗
PubMed1980

The activities of thymidine metabolising enzymes during the cell cycle of a human lymphocyte cell line LAZ-007 synchronised by centrifugal elutriation.

The activities throughout the cell cycle of thymidine kinase (EC 2.7.1.21), dihydrothymine dehydrogenase (EC 1.3.1.2), thymidine phosphorylase (EC 2.4.2.4) and dTMP phosphatase (EC 3.3.3.35) were measured in the Epstein-Barr virally transformed human B lymphocyte line LAZ-007. Cells were synchronised at different stages of the cell cycle using the technique of centrifugal elutriation. The degree of synchrony in each cycle-stage cell population was determined by flow microfluorimetric analysis of DNA content and by measurement of thymidine incorporation into DNA. The activity of the anabolic enzyme thymidine kinase was low in the G1 phase cells, but increased manyfold during the S and G2 phases, reaching a maximum after the peak of DNA synthesis, then decreasing in late G2 + M phase. By contrast, the specific activities of the enzymes involved in thymidine and thymidylate catabolism, dihydrothymine dehydrogenase, thymidine phosphorylase and dTMP phosphatase remained essentially constant throughout the cell cycle, indicating that the fate of thymidine at different stages of the cell cycle is governed primarily by regulation of the level of the anabolic enzyme thymidine kinase and not by regulation of the levels of thymidine catabolising enzymes.

B-Lymphocytes↗
PubMed1980

Cancer chemotherapy--what have we achieved?

The outcome of referral to a medical oncology unit in a university teaching hospital has been determined for the first 500 patients seen in 1978. Their median age was 58 years, and half had been referred within 6 weeks of diagnosis. 316 had already received some form of treatment. Compared with the overall figures for New South Wales, there was an excess of lung cancer, breast cancer, head and neck cancer, ovarian carcinoma, and testicular cancer, but a smaller proportion of gastrointestinal cancers. No treatment was recommended for one-third. Of the 334 treated, 247 received cytotoxic drugs. By Aug. 1, 1979, 56% from the treated group and 52% of the untreated group had died, the median survival times for the two groups being 45 and 35 weeks, respectively. But, of the 50 who received "curative" or "adjuvant" chemotherapy, only 17 had died by Aug. 1, 1979. Serious complications of treatment occurred in 22 (8.8%) patients. The cytotoxic drugs used by the unit between January, 1978, and August, 1979, cost A$212 000 (9.3% of the hospital's total pharmacy budget for the period). The findings suggest that the widespread use of cancer chemotherapy is not justified outside well conducted clinical trials or specialist cancer centres.

Adolescent↗
PubMed1980

Cis-platinum treatment of metastatic adrenal carcinoma.

Cis-platinum was used in the management of four patients with metastatic carcinoma of the adrenal cortex. In each instance, clinical and objective response was observed. This agent would appear to warrant further trial in the management of this rare tumour.

Abdominal Neoplasms↗
PubMed1980

Father-son testicular malignancy. Does genetic anticipation occur?

Testicular malignancy in a father and son is reported. The father had sequential bilateral seminomas while the son had embryonal cell carcinoma and seminoma. Reported cases of father-son testicular malignancy are reviewed and a predominance of seminomas in the fathers is apparent while the sons' tumors are highly malignant teratomas, choriocarcinomas and embryonal cell carcinomas. The possibility of genetic anticipation in father-son testicular malignancy is discussed.

Adult↗