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W Grove

Publications and source records attributed to W Grove.

10 recordsLinked to original sources
PubMed1991

Phase II study of the amsacrine analogue CI-921 (NSC 343499) in non-small cell lung cancer.

CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.

Adult↗
PubMed1990

Treatment of metastatic malignant melanoma with trimetrexate: a phase II study.

Trimetrexate glucuronate, a nonclassical antifolate, was administered to 14 patients with recurrent and progressive metastatic malignant melanoma. Thirteen patients were evaluable for response and toxicity. Five patients had received prior treatment consisting of immunotherapy (one patient), immunotherapy plus radiotherapy (one patient), radiotherapy (one patient), chemotherapy (one patient), or radiotherapy and chemotherapy (one patient). The starting dose of trimetrexate was 8 mg/m2 given as an intravenous bolus daily for 5 consecutive days of a 21-day cycle. Subsequent cycles of therapy were escalated by 25% based on individual patient tolerance. A median of two courses of trimetrexate was administered (range 1-4). No patient demonstrated a measurable objective response to this treatment regimen. Trimetrexate was well-tolerated; toxicity was mild and consisted primarily of myelosuppression or nausea and vomiting. At the dose level and schedule used in this study, trimetrexate was not effective for the treatment of disseminated malignant melanoma.

Adult↗
PubMed1990

3-Deazaguanine: report of a phase I trial and drug-related cardiac toxicity.

3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or gastrointestinal toxicity was observed. Some patients reported brief episodes of burning at the infusion site or transient facial flushing immediately following the administration of dezaguanine. Three patients experienced cardiac toxicity. Two patients, at doses of 1130 and 2000 mg/m2 respectively, developed congestive heart failure. In one case the heart failure was fatal; the second patient recovered within 8 weeks. The third patient had a progressive fall in left ventricular ejection fraction but did not develop clinical evidence of heart failure before his death from progressive cancer two months later. Postmortem cardiac pathology in the two patients who died early following therapy revealed nonspecific interstitial fibrosis without inflammatory cell infiltrates. The myocardium of the third patient, who died 20 months after receiving dezaguanine, was normal. Electron microscopic analysis of myocardium from the first patient did not show myofibrillar loss or mitochondrial disorganization characteristic of anthracycline cardiomyopathy. Due to the probable cardiotoxicity of dezaguanine in this study and the lack of objective antitumor response, further development of this agent has been discontinued.

Adult↗
PubMed1989

Bipolar affective disorder and high achievement: a familial association.

The authors studied 442 probands with nonbipolar major depression, 64 with bipolar II disorder, and 88 with bipolar I disorder. Although the proband groups did not differ in occupational or educational achievement, the first-degree relatives of probands with bipolar disorders had significantly higher mean levels of achievement than did those of probands with nonbipolar disorder. This pattern applied whether or not the relatives themselves had bipolar illness. The authors conclude that the socioeconomic advantage previously associated with affective disorder in general may be limited to the bipolar forms.

Achievement↗
PubMed1988

Phase I trial of the amsacrine analogue 9-[( 2-methoxy-4-[(methylsulfonyl)amino]-phenyl]amino)-N,5-dimethyl-4- acridinecarboxamide (CI-921).

CI-921, an analogue of amsacrine with superior activity against in vivo and in vitro experimental tumor models, has been studied in 16 patients with solid tumors refractory to chemotherapy or for which conventional therapy does not exist. Thirty-nine cycles were given and doses escalated from 39 to 810 mg/m2. This total dose was divided over 3 consecutive days and administered by 15-min infusion each day, repeated three times weekly. Neutropenia (Eastern Cooperative Oncology Group) Grade greater than or equal to 3 occurred at Day 8 (range, 7-13) in 10/13 courses at 648 mg/m2 and in 2/2 courses at 810 mg/m2 with recovery in 10 (range, 4-20) days. At 810 mg/m2 Grade 2 mucositis and phlebitis were noted. Mild nausea and venous irritation occurred in some patients at doses greater than or equal to 288 mg/m2. No objective response was seen. Pharmacokinetics were evaluated following 65 infusions on Days 1 and 3 with plasma concentrations of CI-921 measured by high performance liquid chromatography. Peak plasma concentrations ranged from 3.36 to 85.6 mumol/liter and were significantly correlated with dose. Mean (range) model-independent pharmacokinetic parameters were: distribution half-life, 0.46 h (0.24-1.08); elimination half-life, 2.63 h (1.08-4.98); mean residence time, 2.0 h (1.05-3.35); plasma clearance, 158 ml/h/kg (95-290); and steady-state volume of distribution, 319 ml/kg (219-614) with no significant difference between Day 1 and 3. Toxicity as defined by absolute granulocyte count nadir was significantly correlated with dose, area under concentration-time curve, and peak plasma concentration. The recommended dose for Phase II studies in this schedule is 648 mg/m2 (216 mg/m2 daily for 3 days) repeated every three weeks.

Adult↗
PubMed1988

Trimetrexate and cyclophosphamide for metastatic inoperable nonsmall cell lung cancer.

To determine the maximum tolerated dose (MTD) of trimetrexate glucuronate in combination with cyclophosphamide in patients with metastatic or inoperable nonsmall cell lung cancer (NSCLC), trimetrexate in dosages ranging from 3 to 13.5 mg/m2/day was administered intravenously (IV) to 27 patients for 5 days in combination with cyclophosphamide, 600 mg/m2, on day 1. Patients received between one and six courses of treatment at 3 week intervals, 69 treatment courses in all. Hematological toxicity was mainly mild anemia (81%), leukopenia (67%), and thrombocytopenia (52%). Nonhematological toxicity included nausea and vomiting (67%), mucositis (30%), and urticaria or rash (22%). The incidences of leukopenia and mucositis were dose related. The MTD of trimetrexate in combination with cyclophosphamide was 7.5 mg/m2/day. The dosage chosen for the Phase 2 study, based only on the hematological dose limiting toxicity, was 10.5 mg/m2/day. Of 31 patients with previously untreated metastatic or inoperable NSCLC who have entered in the Phase 2 study, 22 are evaluable for clinical efficacy (World Health Organization criteria, 1979). Treatment was discontinued in four patients because of toxicity. One patient refused further therapy. Four patients are too early to evaluate. Five patients had confirmed partial responses (23%), 12 patients achieved stable disease (54%), and five patients had progressive disease. Results suggest that trimetrexate 10.5 mg/m2/day in combination with cyclophosphamide is active against previously untreated NSCLC. Dose limiting toxicity was mucositis and myelosuppression. An 11 item linear analogue scale assessing quality of life during treatment indicated this combination was well accepted by patients and did not compromise quality of life. The Phase 2 study is continuing.

Adult↗
PubMed1986

Immigration and major affective disorder.

We studied bipolar (ever manic; n = 297) primary unipolar (never secondary; n = 328), and secondary unipolar (n = 241) RDC major affective disorder patients in the NIMH--CRB Collaborative Study of the Psychobiology of Depression--Clinical. We examined rates of immigration, for patients and their parents, in these three diagnostic groups. Primary patients had a twofold increase in the odds in favor of immigration, compared to secondary patients. The difference persisted when proband age was statistically controlled, and could not be accounted for by any difference in sex ratios between groups. Previous findings of an increased rate of immigration in bipolar patients could not be replicated.

Age Factors↗
PubMedDate not supplied

Outcome in RDC schizo-affective depression: the importance of diagnostic subtyping.

A 2-year semiannual follow-up of 40 patients with RDC schizo-affective disorder, depressed type revealed poorer outcomes among those who were subtyped as chronic or mainly schizophrenic patients than among their counterparts with nonchronic or mainly affective schizo-affective depression. Outcomes for these latter groups, in turn, were no worse than those for patients with psychotic major depression. Among a variety of predictors entered into step-wise regression analyses, diagnosis was most important in predicting recovery overall and outcome at 6 months, while demographic variables, particularly sex, predicted outcome at 2 years.

Adult↗