Phase II study of mitoxantrone in patients with mesothelioma: a National Cancer Institute of Canada Clinical Trials Group Study.
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Adult↗
Biomedical subjects
D Raghavan
Publications and source records attributed to D Raghavan.
Initial intravenous cis-platinum therapy: improved management for invasive high risk bladder cancer?
Between August 1981 and December 1983, 50 patients with invasive high risk bladder cancer were treated initially with 100 mg. per m.2 cis-platinum intravenously in 2 doses with a 3-week interval, which was followed by definitive treatment (radiotherapy and/or cystectomy). High risk disease was defined on the basis of at least 2 of the following: invasion into or beyond the muscle (stages B2 to D1), grade III histology, large tumors and ureteral obstruction. Major symptomatic improvement was noted in 38 patients (76 per cent) after 1 to 2 doses of cis-platinum and 30 (60 per cent) had an objective response to cis-platinum. An objective response (complete or partial remission) was noted in 43 patients (86 per cent) after cis-platinum plus definitive treatment. The 12-month actuarial survival was 86 per cent and the 2-year actuarial survival was 80 per cent (although only 14 patients were entered in the study more than 2 years ago). The protocol was well tolerated, with nausea and vomiting being the most common side effects. There were no deaths related to treatment. Ten patients (20 per cent) died of cancer. The relevance of initial cis-platinum therapy in this management program is now being evaluated in a multicenter randomized trial.
Adult↗
Current status and controversies in the management of genito-urinary cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
First-line intravenous cisplatin for deeply invasive bladder cancer: update on 70 cases.
Seventy patients with T2-T4 NX MO bladder cancer were treated with intravenous cisplatin (100 mg/m2 q 3-weekly) followed by radiotherapy and/or cystectomy. Objective responses to cisplatin were seen in 57%. For the first group of 50 patients (treated between August 1981 and November 1983), the actuarial survival rate at 2 years was 64%, with a median survival of 20+ months: 81% of deaths occurred within 18 months of entry. Most relapses occurred in the bladder/pelvis. A randomised, controlled study is in progress to assess the true value of this approach to the treatment of invasive bladder cancer.
Adult↗
Cisplatin, vinblastine, and bleomycin in inoperable non-small cell lung cancer.
Forty two patients with inoperable non-small cell lung cancer were entered into a phase II study of the combination chemotherapy regimen PVB (cisplatin 60 mg/m2 by intravenous infusion over two hours on day 1, vinblastine 4 mg/m2 by intravenous bolus on days 1 and 2, and bleomycin 15 mg intramuscularly on days 1, 8, and 15), repeated at three weekly intervals. Twelve of 40 evaluable patients (30%) achieved partial responses; there were no complete responses. The median duration of response was 16 weeks (range greater than 8-73 weeks). The median survival of responding patients calculated from entry to the study until death (40 weeks) was superior to that of patients failing to respond (15 weeks). Treatment was accompanied by signs of moderate toxicity, particularly myelosuppression, nausea and vomiting, alopecia, and neuropathy. One patient died from a neutropenic infection. PVB is a moderately toxic regimen for non-small cell lung cancer and appears similar in efficacy and toxicity to high dose cisplatin and vindesine.
Adenocarcinoma↗
Intravenous cis-platinum for invasive bladder cancer. Safety and feasibility of a new approach.
The five-year survival rate of patients with locally invasive bladder cancer (stages T3-T4, Nx, Mo) is less than 50% whatever treatment is given. In an effort to improve the prognosis of patients with this disease, we have incorporated into a management protocol two cycles of intravenous administration of cis-platinum before surgery or radiotherapy (which function as the "definitive" treatment). In 10 of the first 12 patients treated, tumour necrosis has been demonstrated histologically, and definite clinical responses have been observed in eight patients after two cycles of cis-platinum treatment. The toxicity has been acceptable, and subsequent management has not been compromised.
Adult↗
Advanced breast cancer: response to high dose oral medroxyprogesterone acetate.
We treated 105 patients with advanced breast cancer, using the progestational agent medroxyprogesterone acetate (MPA), 200 mg orally tds in a non-randomised trial. In general they were a poor risk population, since 78 had received prior endocrine therapy (21 more than one type) and 58 prior chemotherapy. Treatment was well tolerated. Side effects included weight gain, muscle cramps, fine tremor and fluid retention, but these were usually mild, resolved if the dose of drug was reduced, and only one patient stopped treatment because of toxicity. Seventeen patients died within six weeks of starting MPA, and disease progression occurred in a further 58. Nine have had stable disease for periods ranging from two to 11 months, and there were 21 who showed disease regression. Response to treatment continues in 13 of these patients, and at the time of writing the median duration of response is 10 months. Response rates were similar in pre- and post-menopausal patients. The dose of MPA was double to 400 mg tds in 16 patients whose disease had progressed on 200 mg tds, but no additional responses were seen in this group. Seven out of 24 (29%) patients who had not received prior endocrine therapy responded to high dose oral MPA, a response rate similar to that seen following other hormonal manipulations, but because the drug also has activity against hormone-resistant tumours and is well tolerated, it should have role in the treatment of advanced breast cancer.
Antineoplastic Agents↗
Combination therapy with methotrexate and 5-fluorouracil: a prospective randomized clinical trial of order of administration.
Because of biochemical and tissue culture evidence casting doubt on the physiologic relevance of reported synergy afforded by sequential administration of methotrexate (MTX) followed by 5-fluorouracil (5-FU), a randomized controlled clinical trial was conducted in 108 patients with advanced cancer, including 70 with squamous cell carcinoma (SCC) of the head and neck, nine with SCC of other primary sites, 24 with colorectal, and five with gastric adenocarcinomas. Patients were randomized to receive weekly therapy consisting of MTX followed one hour later by 5-FU, or 5-FU followed one hour later by MTX. There was a trend to higher tumor response rates in patients treated with MTX before 5-FU (45% v 33% overall; 65% v 39% in patients with previously untreated head and neck cancer), but these differences were not significant, either by chi-square test or by multivariate stepwise logistic regression. The trend in survival favoring the reverse sequence of 5-FU before MTX was not significant in univariate analyses. Stepwise multivariate Cox model analysis showed that Eastern Cooperative Oncology Group performance status at study entry was the major prognostic factor for survival (P less than 0.001), but among the 70 patients with head and neck cancer, the sequence of drug administration was the only other significant prognostic factor for survival, and favored the sequence of 5-FU followed by MTX (P less than 0.025).
Adenocarcinoma↗
Surgery in patients with advanced germ cell malignancy following a clinical partial response to chemotherapy.
Twenty-one patients with metastatic germ cell tumors achieved only partial clinical tumor regression following chemotherapy, and underwent surgical biopsy or resection of the residual tumor deposits. Sixteen (76%) are at present clinically disease-free after a median 30 + months (range 17-50 months) from the time of surgery, and five (24%) died after 9-29 months. Adverse prognostic signs were the finding of persistent cancer at histopathological examination of the resected tumor masses, and the presence of elevated serum tumor markers at the time of surgery. Postchemotherapy surgery in this setting provides tissue for the prognostically important histopathological examination on which a decision regarding further chemotherapy may be based. In addition, it provides tumor bulk reduction in the cases of differentiated teratoma and persistent cancer.
Adolescent↗
The role of hepatitis B virus in the etiology of hepatocellular carcinoma in Australia.
Fifty-three patients with Hepatocellular Carcinoma (HCC) from three Sydney teaching hospitals were examined for possible evidence of Hepatitis B virus (HBV) infection. Hepatitis Surface Antigen (HBsAg) was positive in 38% of those in whom it was sought, a higher incidence than previously reported in an Australian series. A further 13 patients had antibody to Hepatitis B core (Anti-HBc), but negative HBsAg, confirming past exposure to HBV. Where serum was available evidence of HBV infection was obtained in 62% of patients. It is argued that the incidence of HBV infection may be shown to be higher still with the advent of new technology as applied to HBV assays and tissue stains. The need to be aware of the growing evidence of a strong association between Hepatitis B virus and the development of HCC is stressed and the clinical implications are discussed.
Alcohol Drinking↗
Lorazepam as an adjunct to antiemetic therapy with haloperidol in patients receiving cytotoxic chemotherapy.
Twenty-seven consecutive patients were treated with 3 mg oral lorazepam and 2.5 mg intravenous haloperidol in an effort to improve patient tolerance of cytotoxic chemotherapy and decrease nausea and vomiting. Antiemetic efficacy and side-effects were assessed using a patient questionnaire. Vomiting either did not occur, or was considered to be of only moderate intensity in 22 patients (81%) and usually ceased within 24 hours of commencing chemotherapy. Similarly, nausea was either absent or of only moderate severity, lasting less than 48 hours in the majority of patients. Eight of 11 patients who had received similar previous cytotoxic treatment with antiemetic agents but not lorazepam considered that lorazepam and haloperidol had considerably improved their tolerance of chemotherapy. The side-effects of haloperidol and lorazepam were mild and well tolerated.
Anti-Anxiety Agents↗
Tumor classification and size in germ-cell testicular cancer: influence on the occurrence of metastases.
The influence of local tumor spread (T-classification) and of tumor size on the occurrence of metastases was studied in 241 patients with testicular germ-cell neoplasms. All patients underwent thorough clinical or pathologic staging, or both, and were treated at the University of Minnesota Hospitals. Spread of tumor through the tunica vaginalis (T2) was associated with abdominal lymph node or distant metastases in eight of nine patients. Local tumor extension to the spermatic cord (T4a) was associated with metastatic spread in 29 of 31 men. Tumor size did not appear to correlate with metastatic rate. These findings are an important aid in designing adjuvant therapy trials and in establishing a "no treatment" approach after orchiectomy.
Adolescent↗
Elevated serum alphafetoprotein and seminoma: clinical evidence for a histologic continuum?
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Adult↗
Ultrastructural studies of xenografted human germ cell tumors.
Xenografts have been established in immune-suppressed mice from three embryonal cell carcinomas, two yolk sac carcinomas, and a 'seminoma-like' tumor that produces alphafetoprotein. The ultrastructural features of these xenografts have been studied in detail and compared with human germ cell tumors removed from patients. A spectrum of ultrastructural differentiation has been demonstrated for tumors of the same histologic classification (embryonal cell carcinoma) and within individual tumors. Cells with ultrastructural appearances intermediate between seminoma and yolk sac carcinoma and between embryonal cell and yolk sac carcinoma have been demonstrated, and their potential implications for tumor histogenesis are discussed.
Adult↗
Characterization of a new human cell line derived from a xenografted embryonal carcinoma.
A human cell line has been established from a transplantable xenografted human testicular tumor, which, both in the original tumor and in the xenograft, exhibited the histological characteristics of an undifferentiated malignant teratoma (embryonal cell carcinoma). The cells in culture were undifferentiated by biochemical, morphological, and ultrastructural criteria, growing as small islands of cells that tended to form aggregates at high density. The cells showed some variation in chromosome number with 30 to 40% of the cells having a normal human karyotype. The cells expressed high levels of alkaline phosphatase, which by heat inactivation and inhibition studies was 40 to 50% placental type alkaline phosphatase. None of the cultures produced human chorionic gonadotrophin, alphafetoprotein, carcinoembryonic antigen, or fibronectin, although at high cell densities plasminogen activator could be detected at low levels. Cell surface studies showed that the cells shared antigens with the murine embryonal carcinoma cell line F9, expressed beta 2-microglobulin at very low and variable levels, and bound the lectin peanut agglutinin. These studies suggest that this cell line has some of the characteristics described for murine embryonal carcinoma cell lines.
Alkaline Phosphatase↗
VP-16-213 (etoposide): the mandrake root from Issyk-Kul.
VP-16-213 (etoposide) is an orally and parenterally active antineoplastic agent synthesized from podophyllum extracts of a common North American plant, the May apple or mandrake. The drug delays and kills cells in the G2 phase of the cell cycle and is active in a variety of animal tumors and leukemias. Major therapeutic activity for the drug has been found in small cell bronchogenic carcinoma, germ cell malignancies, acute non-lymphocytic leukemia, Hodgkin's disease and non-HOdgkin's lymphoma. Minor therapeutic activity of the drug occurs in non-small cell bronchogenic carcinoma, pediatric neoplasms, hepatocellular carcinoma and gastric cancer. Toxicity is primarily hematologic, with alopecia, nausea and vomiting occurring less frequently.
Animals↗
Mediastinal nonseminomatous germ cell tumors: the role of combined modality therapy.
Twelve male patients with mediastinal nonseminomatous germ cell tumors were treated with chemotherapy (with or without operation and radiation therapy) between 1963 and 1980. Eight patients, treated with only chemotherapy and radiotherapy, died with a median survival from diagnosis of 6 months (range, 3 to 12 months). The 4 survivors remain alive at 12, 15, 34, and 56 months from diagnosis; all are without evidence of disease. All surviving patients were treated with surgical resection of disease either before of after chemotherapy. A major problem in the management of mediastinal nonseminomatous germ cell tumors is the persistence of local disease, which may be overcome by vigorous cytoreductive intervention. Multicenter collaboration will be required to define the optimal combined-modality approach.
Adolescent↗
Prognostic factors in clinical stage I non-seminomatous germ-cell tumours of the testis.
Prognostic factors have been studied in 59 men with clinical Stage I non-seminomatous germ-cell tumours of the testis (NSGCTT) seen at the Royal Marsden Hospital between 1973 and 1978. Fourteen of the patients relapsed, and 45 have remained continuously disease-free. Two factors were identified which showed a significant correlation with relapse following radiotherapy: local extent of the primary tumour, and rate of decline of serum alpha-foetoprotein (AFP) and beta-human chorionic gonadotrophin (hCG) levels following orchidectomy. High serum marker levels at the time of referral after orchidectomy were not prognostically significant per se. The presence of tissue-associated hCG in the primary tumour was not prognostically significant. The results were compared with histology and pathological stage of the primary tumour in patients presenting with lung metastases but no clinical evidence of lymph-node disease. Embryonal carcinoma was more commonly associated with a locally invasive primary tumour and with extralymphatic spread than was teratocarcinoma.
Adolescent↗