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Biomedical subjects

S B Kaye

Publications and source records attributed to S B Kaye.

At least 325 records · Page 18Linked to original sources
PubMed1986

Short duration combination chemotherapy in the treatment of small cell lung cancer.

Ninety five patients (57 with limited disease and 38 with extensive disease) with previously untreated small cell lung cancer were entered into a study of short duration combination chemotherapy with intravenous cyclophosphamide (750 mg/m2) on day 1, adriamycin (40 mg/m2) on day 1, and etoposide VP-16 (100 mg/m2) on days 1, 2, and 3, with the addition on day 10 of methotrexate 50 mg/m2 with folinic acid rescue and vincristine 2 mg. The treatment was repeated on day 22 and only three courses were given. No maintenance chemotherapy was given, though patients with a complete response received radiotherapy (30-40 Gy (3000-4000 rads] to the primary site in most cases. Forty nine patients (86%) with limited disease achieved a response, with 26 (46%) complete remissions. Twenty five patients (66%) with extensive disease had a response, but only eight (21%) had a complete response. Actuarial survival analysis for the whole patient population showed a median survival of 13 months for patients with limited disease and seven months for those with extensive disease. The median survival was 14 months for those patients with limited disease who achieved a complete response, but only 10 months for non-responders. Myelosuppression was the major expression of toxicity. There were three deaths related to treatment and seven patients had febrile episodes during neutropenia that required antibiotics. Mucositis, which was usually mild, occurred in 49% of patients. The primary site was the main site of initial relapse in 56% of the patients who relapsed. Among patients with limited disease who achieved a complete response, relapses at the primary site were less common in those who received radiotherapy (five out of 12) than in those who did not (all eight). The results indicate that this short duration chemotherapy in small cell lung cancer gives response rates and the potential for long term survival similar to those obtained in other series while allowing patients the maximum time free from treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

High-dose versus low-dose vinblastine in cisplatin-vinblastine-bleomycin combination chemotherapy of non-seminomatous testicular cancer: a randomized study of the EORTC Genitourinary Tract Cancer Cooperative Group.

Two hundred fourteen patients with disseminated non-seminomatous testicular cancer were randomized to receive induction chemotherapy with cisplatin, vinblastine, and bleomycin (PVB). The randomization was for vinblastine 0.4 mg/kg/cycle or 0.3 mg/kg/cycle. The complete response (CR) rates to both regimens were identical: 68% and 71%, respectively. In addition, there was no significant difference in disease-free and overall survival. There was a significant decrease in the incidence of WBC nadirs below 1,000/microL: 29% and 13%, respectively (P = .01). Of the non-hematologic toxicities, there was a significant reduction in the incidence of mucositis: 53% and 37%, respectively (P = .006). The major prognostic factor was tumor volume. This study confirms that vinblastine 0.3 mg/kg/cycle in PVB chemotherapy is as effective and less toxic than vinblastine 0.4 mg/kg/cycle.

Adolescent↗
PubMed1986

Phase I and pharmacokinetic study of LM985 (flavone acetic acid ester).

We have conducted a Phase I and initial clinical pharmacological evaluation of LM985, the first of a series of compounds based on the flavone ring structure to be considered for clinical trial in malignant disease. The drug was administered i.v. to 26 patients with advanced cancer on an every-21-day schedule. Patients were treated at 14 dosage levels ranging from 10 to 1500 mg/m2. Dose limiting toxicity was identified as acute reversible hypotension occurring during drug infusion; no leukopenia, alopecia, hepatic toxicity, or renal toxicity was observed, but at the higher dose range, mild sedation was apparent. Twenty patients had measurable disease and were evaluable for response. One patient with colorectal carcinoma had stable disease after three courses of LM985; however, no other responses were seen. Pharmacokinetic and in vitro drug degradation studies imply that the ester LM985 is hydrolyzed to LM975 (flavone acetic acid) rapidly in vivo. LM975 is active in a variety of animal tumor models, but it does not have the cardiovascular side effects seen with LM985 (hypotension and bradycardia) in pithed or anesthetized rats. We would recommend that LM975 be considered for clinical trial, because it seems likely that substantially higher doses of LM975 than of LM985 can be given without dose limiting cardiovascular toxicity.

Adult↗
PubMed1985

High-dose cyclophosphamide and VP 16 as late dosage intensification therapy for small cell carcinoma of lung.

This study investigated the use of late dose intensification therapy (LDIT) with cyclophosphamide (180 mg/kg) and VP 16 (1 g/m2) plus autologous bone marrow rescue in 22 patients with small cell lung cancer (SCLC). These patients were selected from a group of 95 patients who received three courses of a five-drug induction regimen comprising cyclophosphamide (750-1000 mg/m2), adriamycin (40 mg/m2), VP 16 (100 mg/m2) for 3 days, methotrexate (50 mg/m2) and vincristine (2 mg) (CAVMO). There were 16 patients with limited disease, 8 of whom were in complete remission (CR) and 8 in partial remission (PR) after the induction therapy. The other 6 patients had extensive disease; 3 of these achieved CR and 3 PR after induction therapy. Of the 11 patients in PR, 5 responded to LDIT; 3 had a further PR, and 2 CR. Subsequent to LDIT radiotherapy 4000 cGy was given to the primary site in 10 of the 22 patients. Since the start of the study, 19 of the 22 patients have relapsed and died (median survival 11 months), while 3 remain alive and in remission at 11, 11, and 24 months. Comparison of the survival of patients receiving LDIT with that of an equivalent group (with respect to staging and response to induction chemotherapy) of patients who received induction chemotherapy alone showed no significant difference. In this study, LDIT following conventional induction therapy in patients with chemosensitive tumours did not improve survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

EORTC Genito-Urinary Group studies in advanced testicular cancer--past and future.

Two hundred and twenty-eight patients with advanced testicular cancer were entered into a randomized study of chemotherapy comprising cis-platinum (P) 20 mg/m2-, days 1-5 every 3 weeks for four courses, bleomycin (B) 30 mg weekly for 12 weeks, and vinblastine (V) at either the low dose of 0.15 mg/kg or the high dose of 0.20 mg/kg on days 1 and 2 every 3 weeks for four courses. In this interim analysis, 64 patients were randomized to high dose PVB. Forty-five (71%) achieved a complete response, and 13 (25%) a partial response. Seventy patients received low dose PVB of whom 50 (71%) achieved a complete response and 16 (23%) a partial response. Thus there is no difference in the efficacy of this combination chemotherapy with respect to the dose of vinblastine, but the low dose schedule was less toxic (particularly to bone marrow). It was also apparent that the response rate varied with the volume of metastatic disease, irrespective of the dose of vinblastine. Patients with low volume metastases had a complete response rate (CR) of 88%, while those with high volume had a CR rate of 60%. In a second randomization, 68 patients achieving CR were randomized to receive either 1 year of further (maintenance) chemotherapy with cis-platinum and vinblastine, or no further chemotherapy. One of 37 patients (3%) receiving treatment and 2 of 31 patients (6%) not receiving treatment relapsed, with a follow-up of at least 10 months. Thus maintenance chemotherapy appears not to be necessary in the treatment of advanced testicular cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Chemotherapy before radiotherapy for T3 bladder cancer. A pilot study.

Seventeen patients with stage T3 bladder cancer were treated in a pilot study of initial chemotherapy (four courses of cyclophosphamide, methotrexate and 5-fluorouracil) followed by megavoltage radiotherapy 6000 cGy) to the bladder. Chemotherapy was well tolerated and did not lead to any increase in toxicity from the radiotherapy. Assessment of response in all cases was not possible because of the variable extent of the initial biopsy. Of the 12 patients in whom assessment was possible, there was no objective change in 9 (4 cases of T3a; 5 cases of T3b) and there was objective evidence of disease progression in 3 (2 cases of T3a; 1 case of T3b). Thirteen patients have now died and the median survival for patients in this study was 27 months, with a 3-year survival rate of 26%. Three patients died with recurrence in the pelvis, 5 with both local and metastatic disease, 2 with metastases only, and 3 from other causes. These data indicate that this particular form of chemotherapy given as initial treatment for T3 bladder cancer does not appear to lead to an improvement in the results obtained from radiotherapy alone.

Adult↗
PubMed1984

Treatment of advanced squamous-cell carcinoma of the head and neck with a combination of cisplatin, vinblastine, and bleomycin.

Fifty patients with advanced, measurable, squamous-cell cancers of the head and neck received treatment with a combination of cisplatin, vinblastine, and bleomycin (PVB). The tumours in 25 patients (50%) responded to treatment (partially in 17 and completely in eight). The median duration of response was 18 weeks, and that of survival was 31 weeks. Toxicity was moderately severe; myelotoxicity occurred in 13 patients, and nausea and vomiting in 22 patients.

Adolescent↗
PubMed1984

Advanced gastric cancer: experience in Scotland using 5-fluorouracil, adriamycin and mitomycin-C.

Eighty-four patients with advanced gastric cancer treated in four centres in Scotland between June 1980 and December 1982 were reviewed following treatment with 5-fluorouracil, adriamycin and mitomycin-C (FAM). Eighty-one patients were evaluable. Twenty-eight patients (35 per cent) responded (four complete) with a median duration of response of 10.5 months and median survival of 17 months. Ten are still alive. Response was associated with an improvement in performance status. Eight patients (10 per cent) had stable disease with a median survival of 10 months. Forty-five (55 per cent) had progressive disease with a median survival of 4.5 months; one patient remains alive. Analysis of prognostic variables indicated that the presence of hepatic metastases had a negative influence on response to FAM (P less than 0.001). Treatment was well tolerated on an outpatient basis. FAM offers good palliative therapy in a proportion of patients with this disease, especially those without overt liver metastases.

Adenocarcinoma↗
PubMed1984

The effect of cytotoxic therapy on saliva and oral flora.

Oral complications of cytotoxic therapy result from direct mucosal damage and, indirectly, occur as a consequence of immunosuppression. Such problems are further exacerbated as a result of associated xerostomia and secondary infection. Therefore, the aims of this study were to examine the salivary volume and composition (amylase, IgA, and lysozyme) together with the oral carriage of potential pathogens in patients receiving cytotoxic therapy. A pilot study comparing healthy controls with patients on chemotherapy for malignant conditions indicated that there were differences between the two groups. Therefore, a longitudinal study was initiated and twelve patients were assessed prior to and 4 and 12 weeks after the start of cytotoxic therapy. The 10-minute forced-spitting salivary volume and amylase and IgA levels all declined significantly over the 12-week period. Lysozyme content did not change. A quantitative increase in the oral carriage of Candida species, coliforms, and Staphylococcus aureus was also observed during therapy. Hence, it is concluded that cytotoxic chemotherapy results in a decreased salivary flow, a reduction in salivary amylase and IgA, and an increase in the oral carriage of opportunistic pathogens.

Adult↗
PubMed1984

Vindesine and cisplatin combination chemotherapy compared with vindesine as a single agent in the management of non-small cell lung cancer: a randomized study.

One hundred and five patients with inoperable non-small cell lung cancer were included in a randomized trial comparing the activity of vindesine as a single agent with the combination of vindesine and cisplatin. All patients were previously untreated and the majority (70%) had squamous carcinoma. The overall partial response rates in 88 evaluable patients were 7% for vindesine alone and 33% for the combined regime. There were no complete responders in either arm. The median survival of patients treated with vindesine and cisplatin was 11 months, compared with 4 months in those treated with vindesine alone (P = 0.008). Patients showing a partial or complete response to vindesine and cisplatin survived a median duration of 13 months, compared with 7 months for non-responders (P = 0.03). This survival benefit associated with the combination was particularly apparent for patients with ECOG performance status 0 or 1 (median survival greater than 18 months and 13 months respectively), locoregional disease (median survival 14 months) and squamous cell histology (median survival 13 months). Myelo-suppression was greater with the combination but was not a major treatment problem. Neurotoxicity, which was frequently dose-limiting, was of similar severity in both treatment groups. The results indicate that the combination of vindesine and cisplatin is superior to vindesine alone for remission induction in non-small cell lung cancer and confers a significant survival advantage compared with vindesine alone in patients with favourable prognostic factors.

Adenocarcinoma↗
PubMed1984

The treatment of advanced bladder cancer with methotrexate and cis-platinum--a pharmacokinetic study.

As part of a phase III study in advanced bladder cancer, 5 patients received methotrexate (MTX) 50 mg/m2 as a single agent every 2 weeks, and with every alternate dose of MTX (i.e. every 4 weeks) cis-platinum (CDDP) 50 mg/m2 was given simultaneously, together with saline hydration and diuresis. The clearance of MTX was measured in a total of 12 courses by serial serum sampling for up to 72 hr following injection. In 4 patients (with a mean pretreatment creatinine clearance of 97 ml/min) there was no significant difference between the clearance of MTX when given alone [mean t1/2 (beta) 3.2 hr] and when given 2 weeks later with concurrent CDDP [mean t1/2 (beta) 2.9 hr]. In 1 patient with a pretreatment creatinine clearance of 52 ml/min the clearance of MTX when given alone (without hydration) was significantly delayed compared with the clearance of MTX when given 2 weeks later concurrently with CDDP and saline hydration [t1/2 (beta) 19 and 4.5 hr respectively]. Of the 5 patients so far treated with MTX-CDDP, 2 have had a partial objective response and 3 have had stable disease (including 2 with a marked subjective response). These data indicate that in patients with satisfactory renal function, low-dose MTX and CDDP may be given concurrently without risk of enhanced drug toxicity.

Aged↗
PubMed1984

Response of differentiated but not anaplastic teratoma to interferon.

A Phase 2 trial was conducted using intramuscular lymphoblastoid interferon (IFN, Wellcome Research Laboratories), 4 MU per day, in 10 patients with chemotherapy-resistant teratomas. There was stabilisation of disease in 2 patients both of whom were in retrospect considered to have had differentiated teratoma at the time of IFN administration. There was progression of presumed active anaplastic germ cell tumour in 8 patients. One of these patients, a 15-year-old boy with biopsy proven differentiated teratoma has received 2 courses of lymphoblastoid IFN and 1 course of recombinant leukocyte A IFN (Roche Products Ltd.) lasting 5 1/2, 8 and 8+ months respectively. He has had a mixed response in his differentiated tumour which on each occasion has been maintained for the duration that he received IFN. Rising HCG levels during his second course of interferon required additional cytotoxic chemotherapy. Lymphoblastoid IFN does not appear to be active against anaplastic germ cell tumours but both lymphoblastoid and recombinant leukocyte A IFN may be useful in the treatment of unresectable differentiated teratoma.

Adolescent↗