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Biomedical subjects

D Raghavan

Publications and source records attributed to D Raghavan.

At least 127 records · Page 7Linked to original sources
PubMed1988

A prospective study of cisplatin-based combination chemotherapy in advanced germ cell malignancy: role of maintenance and long-term follow-up.

Two hundred fifty-three patients with advanced germ cell malignancy received initial chemotherapy with cisplatin, vinblastine, and bleomycin followed by surgical resection of residual masses if possible. Patients achieving complete remission (CR) were prospectively randomized to receive 6 months maintenance therapy with vinblastine or no further treatment. CR was achieved in 183 patients (72%) and a further eight patients (4%) had complete resection of residual viable malignancy (no evidence of disease [NED]). Pretreatment factors having a significant adverse influence on response by univariate analysis included extragonadal origin of the tumor, poor performance status, advanced lung or lung and abdominal disease, and elevated serum levels of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) greater than 1,000 ng/mL. Multivariate regression analysis indicated the independent prognostic factors of significance were advanced lung or advanced lung and abdominal disease, total tumor diameter greater than 10 cm, and a serum level of HCG greater than 1,000 ng/mL. Of the toxicities encountered, myelosuppression was significant, being exacerbated by radiotherapy, and seven deaths occurred from septicemia. Bleomycin pulmonary toxicity occurred in 46% of patients and was severe in 4%, resulting in eight deaths. With a median follow-up of 64 months, relapses have occurred in 25 patients with no significant difference between those patients receiving or not receiving maintenance vinblastine. Eight of these relapses occurred beyond 1 year and four beyond 2 years of follow-up. Presently, 68% of the total patient population is alive and disease-free, with 84% of the CR and NED patients alive and 81% alive and disease-free. It is concluded that with prolonged follow-up, vinblastine maintenance therapy does not improve treatment outcome. Moreover, late relapses occur, cautioning against premature pronouncements of cure.

Adolescent↗
PubMed1988

Non-hormone chemotherapy for prostate cancer: principles of treatment and application to the testing of new drugs.

Prostate cancer, one of the commonest malignancies in western society, remains a major challenge in management. Although the typical patient is elderly and may not withstand aggressive approaches to treatment, increasing numbers of our population survive to old age, while remaining healthy and active. As prostate cancer is a disease of old age, it is therefore likely that there will be an increased requirement to combat this disease in a fit patient population. Although hormonal manipulation provides effective first-line treatment for 70%-80% of patients with metastatic disease, the majority of these ultimately relapse. Cytotoxic chemotherapy has not provided a panacea for relapsed, hormone-resistant prostate cancer. Despite the significant subjective and objective responses that can be achieved by the use of single agents, the median survival of patients with hormone-resistant disease remains less than 12 months. The use of combination cytotoxic regimens has not altered this. New approaches, perhaps including the development of new cytotoxic agents, innovative uses of established drugs, or the application of the biological response modifiers will be required before this problem is resolved. Until then, we must not be satisfied with inadequate indices of success. The reporting of response rates and of survival statistics drawn from the small group of responding patients is no true indicator of success. Until truly effective treatment is available, we must learn to define more useful indicators of patient benefit, to be more effective in palliating the symptoms of this disease, and to be more critical of the limitations of our progress.

Antineoplastic Agents↗
PubMed1988

Applications of the xenograft as a model of invasive transitional cell carcinoma of the bladder.

We have established a series of serially-transplantable xenografts of human bladder cancer which encompass the broad range of histological subtypes of this disease. Substantial heterogeneity has been demonstrated with respect to the ultrastructural and functional characteristics of these lines. We have used this model to explore the histogenesis of the different subtypes of bladder cancer as well as for preliminary studies of novel anti-cancer drugs for this disease. Future studies will characterise further the differences between superficial and invasive tumours and may reveal predictors of their natural history and metastatic potential.

Adenocarcinoma↗
PubMed1987

Pharmacokinetics of trimetrexate administered by five-day continuous infusion to patients with advanced cancer.

The disposition of the methotrexate analogue trimetrexate (TMTX, NSC 352122; 2,4-diammino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]qui nazoline) was determined in a Phase I study in 16 patients with refractory or relapsing cancer. The drug was administered by continuous 5-day infusion at doses of 5 to 60 mg/m2/120 h (1-12 mg/m2 daily for 5 days). Plasma and urine collections were made during and after infusion and TMTX levels were quantitated by a specific and sensitive high-performance liquid chromatographic assay. Estimates of pharmacokinetic parameters were similar when determined by either compartmental or noncompartmental methods. There were no significant differences in parameters between the first and second courses of treatment to 10 of the patients. Significant linear relations between TMTX dose and the area under curve of plasma TMTX (r2 = 0.858, P = 0.0001) and the steady-state TMTX plasma level (r2 = 0.764, P = 0.0001) were established. Total TMTX clearance was 30.4 +/- 7.6 (SD) ml/min/m2, renal clearance 7.80 +/- 3.9 ml/min/m2, nonrenal clearance 23.2 +/- 7.1 ml/min/m2, volume of distribution 32.8 +/- 16.6 liters/m2, and terminal half-life 13.4 +/- 7.0 h. The percentage of the trimetrexate dose excreted unchanged in urine ranged from 8.4 to 40.7% (mean, 24.9 +/- 9.2%) and was related to creatinine clearance (r2 = 0.312, P = 0.010). Trimetrexate renal clearance was also related to urine flow (r2 = 0.330, P = 0.008). Trimetrexate pharmacokinetics was linear over the dose range 5 to 60 mg/m2 when given by 5-day continuous infusion to patients but there was evidence of urine flow-dependent renal clearance which requires further examination.

Adult↗
PubMed1987

Xenografted small cell undifferentiated cancer of prostate: possible common origin with prostatic adenocarcinoma.

The first xenograft line of small cell undifferentiated carcinoma of the prostate (UCRU-PR-2) has been established and characterized. The donor tumor and the xenograft share the common morphological and ultrastructural features of small cell undifferentiated carcinoma (including neurosecretory granules) but also elaborate epithelial membrane antigen and carcinoembryonic antigen, in addition to neurone-specific enolase. The line expresses a diploid DNA complement. Androgen and estrogen receptors are not expressed, although prostatic acid phosphatase is present in sera from tumor-bearing mice in low levels. From these studies, we postulate a possible common stem cell origin for adenocarcinoma and small cell undifferentiated carcinoma of the prostate; further studies of a cell line derived from this tumor may clarify the issue.

Acid Phosphatase↗
PubMed1987

Flow cytometric and karyotypic analysis of a primary small cell carcinoma of the prostate: a xenografted cell line.

A human small cell undifferentiated carcinoma of the prostate, xenografted in nude mice, was analyzed both cytogenetically and by DNA flow cytometry. The DNA content of the line indicated its stability on serial passage, and was consistent with the cytogenetic findings. The banded karyotype was hypodiploid with nonrandom losses of chromosomes #6, #7, #10, and #13. Structural rearrangements involved chromosomes #1 and #2, and there were three unidentified markers. The findings were compared with those described in other types of prostatic carcinoma.

Animals↗
PubMed1987

Patient treatment preference in advanced breast cancer: a randomized cross-over study of doxorubicin and mitozantrone.

Twenty-two patients with advanced breast cancer participated in a randomized cross-over study of one cycle each of doxorubicin followed 3 weeks later by mitozantrone or vice versa. Before further treatment, patients selected which drug they wished to continue. Of 18 patients completing the study, 13 chose to continue mitozantrone, 2 doxorubicin and 3 had no preference (P = 0.007). Patients were told to assume similar efficacy of the two drugs and drug preference was based primarily on side-effects. Patient self-assessment of quality of life and physician assigned toxicity scores both indicated that nausea and vomiting, appetite and alopecia were significantly worse following doxorubicin than after mitozantrone. Except for alopecia, no significant period or carry-over effects were noted although the power of the study to detect such interactions was low. This study design may prove useful in enabling patients to select their preference between two treatments of similar efficacy.

Adult↗
PubMed1987

Metastatic adenocarcinoma of unknown primary site. A randomized study of two combination chemotherapy regimens.

Of 101 patients with symptomatic adenocarcinoma or undifferentiated carcinoma of unknown primary site, 95 were evaluable for the effects of two randomized chemotherapy regimens. Forty-eight patients received combination doxorubicin and mitomycin C (DM) and 47 received combination cisplatin, vinblastine and bleomycin (PB). Response rates were not significantly different between the two treatment groups, 42% for DM and 32% for PVB, with an overall response rate of 37.1%. Survival differences for DM and PVB treated groups were not significantly different, with 18 weeks and 25 weeks median survivals respectively. Toxicities were unequal for the two treatment groups with increased haematological toxicity for DM and greater gastrointestinal toxicity for PVB. The authors conclude both therapies were of limited efficacy in the treatment of ACUP patients and emphasize that only symptomatic patients should be considered for such therapies.

Adenocarcinoma↗
PubMed1987

Chemotherapy of advanced colorectal cancer. A randomized trial of sequential methotrexate and 5-fluorouracil.

Fifty-five patients with advanced colorectal cancer were entered into a randomized controlled clinical trial to evaluate order of administration and sequential methotrexate (MTX) and 5-fluorouracil (5-FU) therapy. Patients were randomized to receive either MTX, 250 mg/m2, followed 1 h later by 5-FU, 600 mg/m2, or 5-FU followed 1 h later by MTX in the same doses. Fifty-four patients were evaluable for response, of whom 15 (28%) achieved objective partial tumor response. There were no significant differences between the two sequences in response rate, time to treatment failure, or survival duration. The results of this study do not indicate a clinically significant difference between the two sequences tested, in which MTX preceded or followed 5-FU by 1 h. Determination of the value of these drugs given sequentially at longer intervals must await appropriate controlled trials.

Antineoplastic Combined Chemotherapy Protocols↗
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↗