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Biomedical subjects

D Raghavan

Publications and source records attributed to D Raghavan.

At least 91 records · Page 5Linked to original sources
PubMed1991

Neo-adjuvant (pre-emptive) cisplatin therapy in invasive transitional cell carcinoma of the bladder.

Following 2 pilot studies which showed 57 and 61% response rates to intravenous cisplatin for transitional cell carcinoma of the bladder prior to definitive treatment, the West Midlands Urological Research Group (WMURG) and the Australian Bladder Cancer Study Group (ABCSG) independently began randomised trials to test the survival benefit of neo-adjuvant intravenous cisplatin prior to radiotherapy in T2-T4 M0 transitional cell carcinoma of the bladder. Both trials failed to recruit their target numbers of 250 patients in the West Midlands and 320 in Australia. Since they had similar treatment protocols and eligibility criteria, they were combined in an overview analysis, achieving a total number of 255 patients. Each treatment group was compared with its own control group and the differences were pooled to give an overall result. There was no difference in survival between treated and control patients. The odds ratio was 1.13 with the control groups faring marginally better than the chemotherapy groups. Even with 255 patients the 95% confidence interval of the odds ratio was wide (0.80-1.57). Although there is no clear evidence of a clinically worthwhile benefit from neo-adjuvant cisplatin, this approach must be tested in a larger study using combination treatments with greater activity in metastatic disease.

Aged↗
PubMed1990

Active and pro-plasminogen activator on the surface of human bladder cancer cells derived from a high grade invasive tumour.

Intact UCRU-BL28 cells derived from a high grade invasive human bladder cancer produced both active and pro-plasminogen activator. Following culture of cells in the presence of plasminogen, all of the pro-plasminogen activator was converted to an active form. Cell-surface extracts showed plasminogen activator activity with a molecular mass of 55,000, similar to that of human urokinase. Extracts also contained gelatinase activities with molecular masses of 101,000; 80,000; 74,000 and 70,000 in polyacrylamide gel electrophoresis. These tumour cell-surface proteinases may be involved in invasion and metastasis in human bladder cancer.

Cell Line↗
PubMed1990

Tumour-induced host stromal-cell transformation: induction of mouse spindle-cell fibrosarcoma not mediated by gene transfer.

Tumour-induced host-cell transformation has been addressed by examining human tumours in situ and following xenograft to nude mice. We have found evidence for the transformation of host stromal fibroblasts both in vivo and following the introduction of the tumours to in vitro culture. The in vitro culture of one such xenograft--derived from a human prostatic adenocarcinoma--resulted in the outgrowth of a transformed aneuploid mouse cell line. This transformed line was tumourigenic both in BALB/c nu/nu (nude) mice and in heterozygous nu/+mice, with the morphology of a spindle-cell sarcoma. The cell line did not express human isozymes or human histocompatibility antigens, nor were human chromosomes present. Moreover, human DNA sequences were not detected by human Alu repeat sequence element probing in the transformed cell line grown either in vitro or in vivo. The line contained retroviral long terminal repeat sequences but there was no evidence of proviral activation. These findings indicate that tumour cells may cause transformation of neighbouring stromal cells; that this transformation may proceed in the absence of DNA transfer or activation of endogenous proviruses; and that the means of this observed transformation may involve humoral factors elaborated by the tumour cells.

Adenocarcinoma↗
PubMed1990

Update in the management of prostate cancer.

Prostate cancer remains one of the commonest malignancies in our community, and it appears that its incidence is rising because of the increasing proportion of the aged population. Improved technology, including the development of new tumour markers and tumour imaging techniques, and a gradually increasing community awareness of this disease, may allow earlier diagnosis. In turn, as the proportion of patients presenting with early stage disease increases, improved approaches to the treatment of localized cancer may thus yield increased community cure rates. The mainstay of treatment of advanced disease remains hormonal manipulation. The introduction of the LHRH agonists has provided an alternative to surgical castration, but has not resulted in an improved response rate or survival from first-line therapy. We believe that these agents do not offer a major benefit, when compared with the simple procedure of orchidectomy, notwithstanding the psychological sequelae of castration. With a median survival of less than five years after hormonal manipulation, many patients still require salvage treatment after relapse. New hormonal therapies yield objective and subjective response rates of approximately 15% and 30%, respectively, but the median survival from the time of hormonal failure remains less than one year. Cytotoxic chemotherapy has not provided a panacea, but has shown definite evidence of antitumour activity in this disease. The use of relatively non-toxic single cytotoxic drugs can provide effective palliation of symptoms in up to 40% of patients and may even prolong survival in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1990

Etoposide, carboplatin, cyclophosphamide and vincristine in previously untreated patients with small-cell lung cancer.

The efficacy and toxicity of 120 mg/m2 etoposide and 100 mg/m2 carboplatin given i.v. daily x 3 together with 750 mg/m2 cyclophosphamide and 1.4 mg/m2 vincristine given i.v. on day 1 (ECCO) in a regimen given every 28 days for 6 courses was assessed in 90 (40 limited stage, 50 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to limited-stage patients without progression after 3 courses of chemotherapy. Cranial irradiation with 30 Gy in 10 fractions was given to all patients attaining a complete response (CR). Objective responses were seen in 83% [CR, 60%; partial response (PR), 23%] of patients with limited and 76% (CR, 22%; PR, 54%) of those with extensive disease. The median relapse-free survival for objective responders with limited disease was 13.4 months, with a median of 8.0 months for extensive-stage patients. The median relapse-free survival for patients achieving a CR was 13.4 months, with a median of 7.8 months for those undergoing a PR. The median survival was 13.3 months for patients with limited disease, with a median of 9.6 months for those with extensive disease. The median survival following a CR was 18.2 months, with a median survival of 9.9 months for those showing a PR. The combination was well tolerated, with either no nausea or nausea only (WHO grade 0 or 1) in 56% of patients and minimal mucositis, renal toxicity, neurotoxicity or ototoxicity. Neutropenia measuring less than 1.0 x 10(9) WBC/l (WHO grade 3 or 4) was seen in 74% of patients, with two deaths due to infection occurring during neutropenia. Thrombocytopenia of less than 50 x 10(9) platelets/l (WHO grade 3 or 4) occurred in 24% of patients. ECCO is a new, active, well-tolerated program for previously untreated patients with small-cell lung cancer.

Adult↗
PubMed1990

Clonal analysis of a bladder cancer cell line: an experimental model of tumour heterogeneity.

The continuous cell line UCRU BL 17CL was derived from a human invasive bladder cancer and expresses elements of transitional, squamous and glandular differentiation. Nine clones of this line were established by limit dilution and have been extensively characterised. Only six of these clones grew subcutaneously in nude mice. Of these, three have exhibited local invasion, each in one of five implanted mice. Although all xenografts expressed transitional, squamous and glandular elements, different histological subtypes predominated within each clone. Only clones which grew in nude mice formed colonies in semi-solid medium, and each responded differently to the influence of medium that had been conditioned by the growth of UCRU BL 17CL, suggesting the possible secretion of a growth factor by these cells. The DNA content and lectin binding profiles of the clones also reflected the heterogeneity of the line. UCRU BL 17CL and the nine clones provide a unique model for the study of tumour heterogeneity, progression and differentiation, and the potential autocrine regulation of growth of bladder cancer.

Carcinoma, Transitional Cell↗
PubMed1990

Prostatic cancer with bone metastases: serum alkaline phosphatase (SAP) as a predictor of response and the significance of the SAP "flare".

The predictive value of serum alkaline phosphatase (SAP) and of prostatic acid phosphatase (PAP) for response to treatment (NPCP criteria) was retrospectively assessed in patients with bone metastases from prostate cancer. Fifty-one patients had SAP measured at the start of treatment and at 1 and 2 months. In 31 of these, corresponding PAP levels were also available at each time point. SAP/PAP profiles at 2 months were classified as "increased" (increment 15% or greater), "decreased" (reduction greater than 15%) or "stable", compared with baseline levels. An additional category, SAP "flare", was also identified (SAP increment greater than 15% at 1 month, with subsequent fall at 2 months). There was a strong association between the SAP profile at 2 months and the response category, whereas the PAP profile at 2 months was more weakly associated. Using results from the 31 patients with both SAP and PAP profiles, the level of SAP was significantly better in predicting the category of response (SAP: sensitivity 94%, specificity 79%; PAP: sensitivity 53%, specificity 57%). An SAP "flare" was associated with response in 8 of 12 patients. An increase in SAP at 1 month is therefore a poor guide to progressive disease and should not be used in isolation to discontinue treatment early. The SAP profile is of value as an earlier predictor of response than X-rays or bone scans and is more reliable than the PAP profile in monitoring patients with prostate cancer and bone metastases.

Acid Phosphatase↗
PubMed1990

Phase II trial of carboplatin in the management of malignant mesothelioma.

Thirty-one patients with advanced malignant mesothelioma, previously untreated or having received only one prior cytotoxic regimen, were treated in a prospective, single-arm phase II trial with carboplatin (NSC 241240) at a dose of 150 mg/m2 per day intravenously (IV) for 3 days (450 mg/m2/course). One complete remission and four partial remissions were achieved, yielding an overall objective response rate of 16% (95% confidence interval [CI], 5.4% to 34%). The median duration of remission was 8 months (range, 5 to 17). Nonhematological toxicity was mild (only 12% with World Health Organization [WHO] grade 3 vomiting); 16% suffered WHO grade 3 to 4 hematological toxicity, but there were no life-threatening episodes and no treatment-related deaths. Carboplatin has modest activity against malignant mesothelioma and, because of its low toxicity, has a role in the management of this disease.

Adolescent↗
PubMed1990

Lack of late toxicity in patients treated with cisplatin-containing combination chemotherapy for metastatic testicular cancer.

To date, the prevalence and nature of the late toxicity of cisplatin-based combination chemotherapy for advanced testicular cancer has been poorly documented. Thirty men with a median age of 35 years (range, 23 to 63), who had undergone such treatment were assessed with detailed investigation to determine the type and frequency of chronic toxicity. The median follow-up from the time of commencement of chemotherapy was 75 months (range, 48 to 126). The most common late toxic effects were high tone hearing loss in 23 men (77%) and electrophysiological evidence of peripheral nerve damage in 15 (50%). Both the hearing and nerve abnormalities were predominantly asymptomatic. In addition, elevation of serum cholesterol, noted in 20 patients (67%), was significant (P = .014) when compared with a control population. Hyperuricemia was present in nine patients (30%). Only one patient, with other risk factors (smoking, family history), had evidence of ischaemic heart disease while 20% (all with a smoking history) had a diminished single breath diffusing capacity for carbon monoxide (DLCO). Cisplatin-based chemotherapy is relatively free of major long-term side effects and should not be withheld for fear of late toxicity.

Adult↗
PubMed1990

Effective salvage chemotherapy with etoposide, dactinomycin, and methotrexate in refractory germ cell cancer. Australasian Germ Cell Trial Group.

Fifty-one patients with advanced germ cell malignancy who had either failed to achieve complete remission with initial cisplatin, vinblastine, and bleomycin chemotherapy or who had relapsed after complete response (CR) to this therapy and then proven refractory on retreatment, were treated with etoposide (75 mg/m2 for 3 days), dactinomycin (1 mg/m2 day 1), and methotrexate (30 mg/m2 day 1) (EAM) every 3 weeks. Courses were continued until maximum response without empirical limit, and if complete remission was achieved, two courses of consolidation therapy were given before cessation of treatment. Thirteen patients (25%) were complete responders with residual masses containing fibrosis or benign teratoma being subsequently resected in seven patients. Two patients had persisting viable carcinoma within residual masses that were completely resected, leaving no evidence of disease (NED); the combined CR plus NED rate was 29%. The only pretreatment factor significantly influencing this response rate was tumor volume. Toxicities were moderate, with leukopenia being observed in 28% of patients, but it was severe in only 2%. There was one death from septicemia. Severe nausea and vomiting occurred in only 9% of patients and treatment-related stomatitis was observed in 42%. All patients achieving CR plus NED have been followed for a minimum of 5 years and no relapses have occurred, suggesting that these patients are cured. Unlike other regimens of salvage chemotherapy, this treatment program did not contain cisplatin and it is contended that a completely noncrossresistant drug regimen based on etoposide provides the opportunity to further improve the curability of patients with advanced germ cell cancer.

Antineoplastic Combined Chemotherapy Protocols↗