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Biomedical subjects

L Holden

Publications and source records attributed to L Holden.

41 records · Page 3Linked to original sources

Developments in chemotherapy for medium- and high-risk patients with gestational trophoblastic tumours (1979-1984).

Identification of various prognostic factors at the start of chemotherapy allows patients with gestational trophoblastic tumours to be categorized into low-, medium- and high-risk groups so that they can be given the minimum treatment necessary to eliminate their disease. Most patients in the low-risk category can be treated with minimal toxicity using a methotrexate/folinic acid regimen and these patients are not considered in this report. Before 1979 patients in the medium-risk category were treated with a sequence of drugs which included, hydroxyurea, methotrexate, 6-mercaptopurine, actinomycin D, vincristine and cyclophosphamide. Since 1979 etoposide has been substituted for vincristine and cyclophosphamide. The 76 patients treated between 1979 and 1983 are all alive and in remission 1.1.85. Three patients (4%) relapsed and required retreatment and all are in remission. Fifty-six patients in the high-risk group, most at risk of developing drug resistance, were treated with a regimen incorporating etoposide with methotrexate, actinomycin D (EMA) and vincristine and cyclophosphamide (CO). EMA and CO were given on alternate weeks, resulting in an overall survival rate of 84%. Patients who had received prior chemotherapy had a survival rate of 74% and a relapse rate of 19% compared with 93% survival and 3% relapse rate in those who had not received prior chemotherapy. Toxicity with the EMA/CO regimen was significantly less than with an earlier regimen (CHAMOCA) used in the high-risk group.

Adult↗

Tumour markers and POMB/ACE chemotherapy in the management of ovarian germ cell tumours (GCTs).

The management of ovarian germ cell tumours (GCTs) has changed dramatically over the last 15 years. The combination of the introduction of tumour markers which accurately monitor the behaviour of the majority of germ cell tumours together with the introduction of newer chemotherapeutic agents has meant that few patients even with metastases should succumb from their disease. The tumour markers, human chorionic gonadotrophin (hCG) and alpha-foetoprotein (AFP) and, to a lesser extent, lactate dehydrogenase (LDH) and placental alkaline phosphatase (PLAP) are routinely used in assisting diagnosis, monitoring response to treatment and increasing the sensitivity of follow-up of patients after completing treatment. Analysis of our last 51 patients with all cell types of ovarian germ cell tumour has confirmed the importance of both hCG and AFP in that 45 (88%) of 51 patients had either or both of these tumour markers raised at the start of treatment for metastatic disease. Our data on LDH is incomplete since this has not been a routine assay until 1984 and, of the patients with active disease 10 (48%) had raised LDH at the start of treatment. PLAP has also been measured in a number of patients both on active treatment and in remission. 11 (50%) had raised levels of PLAP at the start of treatment but there was also a false positive rate of 8 (24%) of the 33 patients who were in remission and had not subsequently relapsed.

Alkaline Phosphatase↗

Refractory studies in early detection of carpal tunnel syndrome.

We studied refractory periods of the median sensory nerves in 10 patients with mild carpal tunnel syndrome (CTS), and compared them with the median sensory refractory studies on normal subjects. Our data showed that relative refractory period (RRP) studies are useful in diagnosing early CTS.

Adult↗

Phase I clinical trial of mitozolomide.

Mitozolomide (NSC-353451; CCRG 81010; M and B 39565) is a novel potential anticancer agent that was selected for phase I study on the basis of broad spectrum activity in mouse tumors. Initially, mitozolomide was given iv as a short infusion to 37 patients in doses ranging from 8 to 153 mg/m2. Nausea and vomiting was dose-related but was not severe. The dose-limiting toxic effect was thrombocytopenia at doses greater than 115 mg/m2, and recovery from the thrombocytopenia was delayed up to 8 weeks. Partial responses were seen in two patients with adenocarcinoma of the ovary. The pharmacokinetics of mitozolomide showed that the half-life of the intact drug in the plasma was between 1 and 1.3 hours. The area under the curve was proportional to the dose administered. Mitozolomide is well-absorbed; therefore, future studies are recommended using a single-dose schedule orally or iv. In the phase I study reported here, a dose of 115 mg/m2 appeared to be safe, but additional studies have shown that when given orally to an older population, most patients experienced thrombocytopenia less than 50,000 cells/mm3. The recommended dose using current data is 90 mg/m2 iv or orally.

Administration, Oral↗