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Biomedical subjects

D Raghavan

Publications and source records attributed to D Raghavan.

At least 145 records · Page 8Linked to original sources
PubMed1987

Chemotherapy for small cell lung cancer: induction and reinduction with VOCA.

Sixty-five patients with small cell lung cancer were treated with VP16, vincristine, cyclophosphamide, and doxorubicin (VOCA) intravenously at three-week intervals. Patients with limited disease received four cycles with responders receiving radiation to the primary site and prophylactic cranial irradiation. Patients with extensive disease received chemotherapy only. Of 59 patients evaluable for chemotherapy response, eight (14%) achieved complete remission and 30 (51%) partial remission. Major side-effects included myelosuppression, alopecia, nausea, and vomiting. Reinduction with VOCA at relapse yielded objective or subjective response in four of seven patients. This regimen is active in small cell lung cancer and was well tolerated by patients. Reinduction of response was possible in a small number of patients retreated and may provide useful palliation for those who relapse when treatment is discontinued.

Adult↗
PubMed1987

Aminoglutethimide in advanced prostatic carcinoma.

We have treated 34 patients with advanced prostate cancer, resistant to orchiectomy or oestrogen therapy, with aminoglutethimide. Seven patients (21%) showed improvement in pain and performance status for prolonged periods. By NPCP criteria six patients had stable disease and one had partial tumour response. Six of these patients remained on oestrogen therapy. Suppressed gonadotrophin levels (FSH and LH), despite orchiectomy, correlated strongly with benefit from aminoglutethimide. No relationships between response to treatment and changes in serum testosterone, dehydroepiandrosterone, oestradiol or prolactin were found. Six patients had side effects requiring cessation of therapy. A further 27 patients developed less severe toxicity. Despite its toxicity, these results show that aminoglutethimide has a role in the management of advanced prostatic cancer resistant to primary hormonal manipulation.

Aged↗
PubMed1987

Phase II study of megestrol acetate for metastatic carcinoma of the prostate.

Forty-three males with recurrent and metastatic cancer of the prostate were treated with megestrol acetate (160 mg/day orally) after having failed first-line hormonal treatment (orchiectomy or diethylstilboestrol). Thirty-seven patients were evaluated objectively for response, 28 of whom received the drug for more than 6 weeks. One patient had a partial response (National Prostatic Cancer Project criteria) and seven had stable disease. Toxicity was usually mild, although five patients developed a transient rise in liver enzymes and one patient had a grand mal fit. Three patients showed evidence of tumour "flare". Megestrol acetate has only limited efficacy in patients previously treated for prostatic cancer by hormonal manipulation.

Aged↗
PubMed1987

Improved survival after brain metastases in non-seminomatous germ cell tumours with combined modality treatment.

Long-term disease-free survival (78 + and 31 + months) has been achieved in two of four patients treated for brain metastases from non-seminomatous germ cell tumours between 1980 and 1984. The incidence of cerebral metastases among 101 patients seen over the 5-year period was 4%. The encouraging results from the use of combined modality treatment, incorporating cisplatin-based chemotherapy, whole brain irradiation and surgery, are reviewed.

Adult↗
PubMed1987

Carboplatin (CBDCA, JM-8) and VP-16-213 in previously untreated patients with small-cell lung cancer.

The efficacy and toxicity of carboplatin 100 mg/m2, administered intravenously (IV) daily X 3, and VP-16-213 120 mg/m2, IV daily X 3, administered every 28 days for six courses, was assessed in 94 (36 limited stage, 58 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to all limited-stage patients with a complete (CR) or partial response (PR) after three chemotherapy courses. Cranial irradiation was administered to all patients with CR. Objective responses were seen in 77% (CR 40%, PR 37%) of patients with limited-stage and 58% (CR, 9%; PR, 49%) with extensive-stage disease. Median relapse-free survival for objective responders with limited stage was 14.6 months and 7.9 months for extensive-stage patients. Median relapse-free survival following CR was 15.4 months and 8.5 months for PR. Median survival was 15.3 months for limited-stage and 8.1 months for extensive-stage patients. The combination was well tolerated with mild nausea or less (World Health Organization [WHO] grade 0 or 1) in 62% of patients and minimal mucositis, renal, neurotoxicity, or ototoxicity. Neutropenia less than 1.0 X 10(9)/L (WHO grade 3 or 4) was seen in 63% of patients, with two deaths from infection while neutropenic. The combination of carboplatin and VP-16-213 is a new, active program with low toxicity when applied intensively in previously untreated patients with small-cell lung cancer.

Adult↗
PubMed1987

Mitomycin and mitoxantrone in previously treated patients with advanced breast cancer.

A total of 56 heavily pretreated patients with advanced breast cancer were treated with the combination mitomycin and mitoxantrone. Partial responses were seen in ten of 56 patients (18%), or ten of 44 (23%) completing two courses, while 18 (32%) had stable disease. Responses were seen in eight patients failing doxorubicin. The median duration of response was 26 weeks, with responders surviving a median of 37 weeks. A total of 59% of the courses were associated with World Health Organization grade 3 or 4 neutropenia (less than 1.0 X 10(9) cells/L). Nausea and vomiting were minimal. Mitomycin and mitoxantrone has activity in heavily pretreated patients with advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Phase I study of epirubicin given on a weekly schedule.

Epirubicin was studied in a phase I setting to find the maximum tolerated dose when given weekly for 3 of 4 weeks. Forty-one evaluable patients were treated in groups at doses increasing from 20 to 45 mg/m2. The highest dose level produced the maximum degree of myelosuppression (lowest neutrophil count, 1.9 X 10(9)/L; range, 0-3.7) recorded on Day 22. This was well-tolerated in this group of mainly pretreated patients. Nonhematologic side effects were minimal. This dose schedule allows a greater dose per unit time to be administered than other recommended schedules for epirubicin.

Adult↗
PubMed1986

Randomised comparison of procedures for obtaining informed consent in clinical trials of treatment for cancer.

Methods of obtaining informed consent have evolved differently in Western countries without substantive information on the impact of these different practices on the patients. A randomised study was performed to compare two commonly adopted methods of seeking consent to randomised treatment: an individual approach at the discretion of each doctor and a uniform policy of total disclosure of all relevant information. The impact of both consent procedures on the patient's understanding and anxiety levels and on the doctor-patient relationship was assessed by means of a questionnaire given soon after the consent interview. Fifty seven patients were assigned at random to two groups: to 29 patients an individual approach to seeking consent was adopted and to 28 patients all relevant information was given. Seven patients refused consent to randomised treatment, with slightly more refusals by patients in the total disclosure group (5 v 2, p = 0.25). The main effects of total disclosure of all information compared with an individual approach to seeking consent were: a better understanding of treatment and side effects and of research aspects of the treatments; less willingness to agree to randomised treatment; and increased anxiety. No significant differences were found in patients' perceptions of the doctor-patient relationship. A repeat questionnaire given three to four weeks later no longer showed significant differences between the two groups.

Anxiety↗
PubMed1986

Danazol treatment of advanced prostate cancer: clinical and hormonal effects.

Danazol was administered to 19 patients with advanced prostate cancer. These patients were treated for periods ranging from 3 days to 18 weeks. There were no objective remissions, but three patients (15.8%) had objectively stable disease (N.P.C.P. criteria) with complete pain control for periods ranging 15-18 weeks. Seven patients experienced tumor flare reactions, one requiring withdrawal of treatment and one resulting in rapid clinical deterioration and death. Four other patients died within 3 weeks and, although they were already in the terminal phase of disease when treatment commenced, it is possible that the deaths were treatment related. This study indicates that danazol has only limited activity in the treatment of advanced prostate cancer and is associated with a high incidence of tumor flare reactions with the risk of rapid clinical deterioration.

Aged↗
PubMed1986

Phase I and pharmacokinetic study of tiazofurin (NSC 286193) administered by 5-day continuous infusion.

A phase I and pharmacokinetic study of tiazofurin (NSC 286193), a C-nucleoside that inhibits IMP dehydrogenase, has been completed. The drug was administered by continuous infusion over 5 days. The maximum tolerated dose was 1650 mg/m2 per day, neurological toxicity being the dose-limiting factor. Gastrointestinal and hematological toxicity were mild. A definite relationship exists between dosage and steady-state levels. The plasma clearance was 29.13 (+/- SD 4.05) ml/min per m2. No complete or partial remissions were demonstrated among the 18 patients treated at five dose levels between 550 mg/m2 and 2200 mg/m2 per day.

Adult↗
PubMed1986

Chemotherapy in metastatic melanoma: phase II studies of amsacrine, mitoxantrone and bisantrene.

In a phase II study 20 patients with measurable metastatic melanoma were treated with amsacrine 120 mg/m2 every 3 weeks. No objective responses were observed. In a separate study 29 patients received mitoxantrone 12-14 mg/m2 every 3-4 weeks. One objective partial response was seen. The drug was well tolerated. Seventeen patients were treated with bisantrene 135-200 mg/m2 weekly. No objective responses were observed. Phlebitis was the major non-hematologic toxicity of bisantrene. These agents are not recommended for treatment of malignant melanoma.

Aminoacridines↗
PubMed1986

Bladder cancer xenografts: a model of tumor cell heterogeneity.

Twenty bladder biopsies from patients with primary transitional cell carcinoma were inoculated into nude mice. To date, eleven of these have grown as primary implants and three serially transplantable xenograft lines (UCRU-BL-12, UCRU-BL-13, UCRU-BL-14) have been established. The histological and ultrastructural features of human transitional cell carcinoma have been maintained in each line. Despite a relatively uniform histological appearance, several indices of occult tumor heterogeneity have been revealed. Immunocytochemical staining was negative for beta-subunit human chorionic gonadotrophin but positive for carcinoembryonic antigen only in areas of squamous differentiation. All three tumors bound peanut lectin. Flow cytometric DNA analysis of UCRU-BL-13 showed multiple aneuploid peaks, separate populations being demonstrated in different xenografts of the same generation. However, the morphologies of these tumors remained identical. On initial implantation UCRU-BL-12 and UCRU-BL-14 were near diploid but aneuploid populations became apparent with increasing passage number. Each xenograft line caused cachexia in the host mice. Treatment with the cisplatin analogue, isopropyl platinum, ameliorated the cachexia displayed by mice carrying UCRU-BL-14 but did not cause tumor regression. UCRU-BL-12, when tested with cisplatin, isopropyl platinum, and carboplatin, showed equivalent growth retardation with each drug. These xenografted human bladder cancers may be useful models for the study of heterogeneity of the tumor populations in bladder cancer and for the evaluation of new approaches to treatment.

Adult↗
PubMed1986

Experimental models of bladder cancer: a critical review.

We have reviewed critically the available models of bladder cancer, and have attempted to compare their strengths and weaknesses where appropriate data are available. Further direct comparisons of the applications of each model will be needed in order to rank them, and to identify areas of research where each model will predominate. Furthermore, more information will be needed to validate each model in the context of human disease. With the increasing range and sophistication of the tools of molecular biology, a very important future direction will be the characterisation of animal and human bladder cancer, and in particular the study of the changes from normal to neoplastic urothelium: tumor markers, chromosomal patterns and oncogenes that are associated with specific biological functions, such as invasion, metastasis and ultimate prognosis. The transfection of normal tissues by oncogenes to yield transformed or immortalised lines may be of critical importance in identifying the nature of neoplastic transformation. The use of animal tumors and xenografts, each with the availability of a physiological internal milieu (although different from human metabolic conditions) may yield useful systems for the testing of new therapeutic approaches. However, of the utmost importance is the continuing need to characterise and validate each model, to avoid multiple publications and nomenclatures pertaining to common lines, and to recognise the limitations of the heavily adapted long term cell lines in vivo and in vitro. The major deficiencies of the available lines continue to be found in the method of their application to basic research, rather than being inherent in themselves. Although there are many theoretical and practical applications of these models, it should not be forgotten that the direct study of human bladder cancer, including the appropriate processing of biopsy specimens, will remain integral to understanding the biology of this disease.

Animals↗