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Biomedical subjects

R Birch

Publications and source records attributed to R Birch.

At least 145 records · Page 8Linked to original sources
PubMed1989

Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol.

Four courses of PVP16B (cisplatin plus etoposide [VP-16] plus bleomycin) has been standard chemotherapy for disseminated germ cell tumors at Indiana University and the Southeastern Cancer Study Group (SECSG) since 1984. We began a random prospective phase III study in patients with favorable-prognosis (minimal and moderate extent) disseminated germ cell tumors comparing four courses of PVP16B over 12 weeks to the identical dose PVP16B administered in three courses over 9 weeks. The categories of minimal and moderate disease constitute approximately two thirds of all disseminated germ cell tumors that require chemotherapy. One hundred eighty-four patients entered this trial, and all patients have a minimal follow-up of 1 year. Overall, 106 of 107 (99%) minimal extent and 73 of 77 moderate patients (95%) achieved an initial disease-free status (NED), confirming the favorable prognostic categories. Eighty-six of 88 patients (98%) randomized to three courses and 93 of 96 randomized to four courses (97%) of PVP16B achieved disease-free status. There have been ten relapses (5%), with five on each arm. Currently, 81 of 88 (92%) and 88 of 96 (92%) patients randomized to three v four courses of PVP16B are continuously disease-free. This study confirms the high cure rate with PVP16B in favorable-prognosis germ cell tumors. The deletion of the fourth course of PVP16B significantly reduces the toxicity, cost, and inconvenience of this curative regimen. We conclude that three courses of PVP16B is the preferred regimen for favorable-prognosis germ cell tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Phase I trial of mitomycin C immunoconjugates cocktails in human malignancies.

Nineteen patients with refractory solid malignancies received individualized combinations of mitomycin C conjugated murine monoclonal antibodies selected by immunohistochemical and flow cytometric screening of tumor specimens. There were no responses in this Phase I study. Thrombocytopenia precluded escalation above a mitomycin C dose of 60 mg per treatment cycle. Preclinical, clinical, and toxicity experiences with this investigational approach to the treatment of cancer are discussed.

Adult↗
PubMed1989

Multiple cycles of constant infusion recombinant interleukin-2 in adoptive cellular therapy of metastatic renal carcinoma.

Twenty patients were treated with metastatic renal cell cancer with 5-day cycles of constant infusion recombinant interleukin-2 (rIL-2) at 3 X 10(6) U/m2/day and with infusion of in vitro activated autologous mononuclear cells. The initial eight patients completed all rIL-2 and cellular therapy in a single 25-day treatment period. The subsequent 12 patients entered a 6-month treatment program involving two separate 15-day cycles of cellular therapy followed by four monthly cycles of maintenance rIL-2. Among eight patients in the 25-day treatment program, there were two with partial response (PR) and one with minor response (MR). None of these responses exceeded 2 months in duration. Among the 12 patients undergoing recycling of therapy, there were two with complete response (CR), two with PR, and one with MR. All four patients with CR or PR in this group demonstrated continuing response with recycling of treatment and none relapsed while receiving maintenance interleukin-2. Three remain in remission at 10, 11, and 12 months. These pilot data confirm that patients can tolerate multiple cycles of adoptive immunotherapy involving constant infusion rIL-2 and suggest that recycling of therapy is necessary to achieve clinically meaningful results.

Adult↗
PubMed1988

Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12. Report of a preliminary randomized, double-blind intervention trial.

To test whether changes in folate and vitamin B12 nutrition modify the severity of potentially premalignant lesions identified by cytology in sputum samples of smokers, we conducted a randomized, controlled prospective intervention trial in smokers with bronchial squamous metaplasia. Seventy-three men with a history of 20 or more pack-years of cigarette smoking who had metaplasia on one or more sputum samples were stratified according to smoking level and randomly assigned to four months' treatment with either placebo or 10 mg of folate plus 500 micrograms of hydroxocobalamin. Direct cytological comparison of the two groups after four months showed significantly greater reduction of atypia in the supplemented group. This provides preliminary evidence that atypical bronchial squamous metaplasia may be reduced by supplementation with folate and vitamin B12. However, the significance of these findings is tempered by substantial spontaneous variation in sputum cytologies, the small study population, the short duration of the trial, and the supraphysiological doses of folate and B12 used. The results should not be construed as pointing to a potential way of preventing lung cancer in individuals who continue to smoke or as supporting self-medication with large doses of folate or B12 by smokers.

Bronchi↗
PubMed1988

Randomized phase II evaluation of iproplatin (CHIP) and carboplatin (CBDCA) in lung cancer. A Southeastern Cancer Study Group trial.

Cisplatin-containing regimens have shown activity in both small and non-small cell lung cancer. We therefore conducted a randomized Phase II trial of the new platinum congeners iproplatin and carboplatin in bronchogenic carcinoma. The overall response rate in chemotherapy-naive non-small cell patients with iproplatin was 3/48 (6%; 95% confidence interval 2-18%) and with carboplatin 6/50 (12%; 95% confidence interval 5-25%). The response rates in previously treated small cell patients were 0/16 and 1/18, respectively. Overall, neither agent has pronounced activity in bronchogenic carcinoma.

Adult↗
PubMed1988

Cisplatin plus etoposide consolidation following cyclophosphamide, doxorubicin, and vincristine in limited small-cell lung cancer.

From June 1982 through October 1985, the Southeastern Cancer Study Group randomized patients with limited small-cell lung cancer (SCLC) to cyclophosphamide plus doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) plus vincristine (CAV) for six cycles v CAV plus concomitant thoracic irradiation as induction therapy. Patients achieving either a complete or partial response and remaining in remission after completion of induction therapy were subsequently randomized to consolidation chemotherapy consisting of cisplatin 20 mg/m2 X 4 plus etoposide (VP-16) 100 mg/m2 X 4 every 4 weeks for two courses v no further therapy. There were 160 patients entered on the consolidation phase and 148 were fully evaluable. The median survival for patients randomized to cisplatin plus VP-16 (PVP16) from start of CAV chemotherapy was 97.7 weeks, compared with 68 weeks for the no-consolidation arm (P = .0094). PVP16 consolidation also significantly increased the duration of remission, with median durations of 49 weeks v 28 weeks (P = .0008). The median durations for partial remission were 41 weeks v 23 weeks (P = .013), and for complete remission, 52 weeks v 30.5 weeks (P = .0091). Furthermore, 18 patients on PVP16 consolidation remain in a continuous complete remission for 12+ months and 13 of these are continuously disease free 2+ years. Eight patients randomized to no consolidation remain in a continuous complete remission, with only four patients disease free 2+ years. PVP16 consolidation has significantly improved the duration of remission and overall survival and appears capable of improving the cure rate in limited SCLC.

Adult↗
PubMed1988

Operations to restore elbow flexion after brachial plexus injuries.

We have reviewed 50 patients at a mean period of 2.7 years after operations to restore elbow flexion lost as a result of traction injuries of the brachial plexus. A variety of operations were used and, in general, patient satisfaction was high. Objectively, however, the power in the transferred muscles was poor; less than half of the patients had a significant improvement in function. Poor control of the shoulder often compromised the result. Latissimus dorsi and triceps transfers proved most reliable, and some Steindler flexorplasties also gave satisfactory results. Pectoralis major transfers were disappointing and we do not recommend their use in women.

Adolescent↗
PubMed1988

Vascular effects of clonidine in patients with tetraplegia and unilateral brachial plexus injury.

Evidence from studies in both animals and in tetraplegics with complete cervical spinal cord transection and preganglionic lesion, indicates that clonidine lowers blood pressure predominantly by a centrally mediated action. We have investigated the haemodynamic basis of this action and performed additional studies in patients with unilateral brachial plexus injury and postganglionic lesions, to further determine the site and mechanism of its action. Blood pressure fell after clonidine in normal subjects but not in tetraplegics. In normal subjects, the fall in blood pressure was associated with a fall in cardiac output, due to a fall in both heart rate and stroke volume. Digital skin vasodilatation occurred after clonidine in normal subjects and only in the innervated limb in patients with unilateral brachial plexus injury. In tetraplegics and in the denervated limb in unilateral brachial plexus injury, there was no vasodilatation; instead a vasoconstrictor response occurred, due to the peripheral adrenoceptor action of clonidine. We conclude that the fall in blood pressure and cardiac output in normal subjects after clonidine were due to its central sympatholytic action. Digital skin vasodilatation after clonidine in normal subjects and the innervated limb in unilateral brachial plexus injury was due to the withdrawal of vasoconstrictor tone and requires intact descending sympathetic pathways.

Adult↗
PubMed1988

Patterns of failure in combined chemotherapy and radiotherapy for limited small cell lung cancer: Southeastern Cancer Study Group experience.

In this analysis, we compare the patterns of failure in the first 12 months for 660 eligible patients randomized to two Southeastern Cancer Study Group (SECSG) protocols for limited extent, small cell carcinoma of the lung between 1978 and 1985. In each protocol, a different schedule of radiotherapy was given in conjunction with combination chemotherapy and was compared with combination chemotherapy alone. In protocol 78 LUN 328, radiotherapy was given between courses of chemotherapy, and in protocol LUN 81343, it was given simultaneously. The rates of local failure, either as an initial or subsequent site, in the first 12 months were significantly lower when thoracic irradiation was given than when it was not (P less than .01). When the 2 radiotherapy arms were compared, there were no significant differences in the rates of local failure alone, but a smaller proportion of patients developed both local failure and distant metastases (P less than .01) when simultaneous radiotherapy was administered. Survival on all 4 arms was similar during the first 2 years of patient study. After 2 years, both radiotherapy regimens showed a trend toward improved survival compared with the combination drug alone (cyclophosphamide, doxorubicin, vincristine) arms. On both protocols, survival from 12 months was significantly longer for those with local control at 12 months than for those who did not show local control.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Experience with the free vascularized ulnar nerve graft in repair of supraclavicular lesions of the brachial plexus.

The treatment consisted of a free vascularized ulnar nerve graft in 63 patients with lesions of the supraclavicular brachial plexus. Since 1978, the outcome in 42 patients with a minimum follow-up period of 30 months was certainly better than with an avascular segment of ulnar nerve. Clear proof of hopeless prognosis for recovery along the course of the ulnar nerve is essential before using this graft. The early operations used the ulnar artery and accompanying veins as the pedicle for the graft; later a technique using collateral vessels in the arm has been favored. Although functional elbow flexion has been regained in the majority of patients, recovery of function into the hand has been disappointing. Although it cannot be proved that results are better than when conventional sural nerve grafts are performed, the authors believe that this is the case. The vascularized ulnar nerve graft (VNG) is indicated in more severe injuries of the brachial plexus, where preganglionic injury to the eighth cervical and first thoracic nerves is proven, where the gap between nerve stumps is long, and when the presence of two or three proximal stumps allows the opportunity for extensive repair.

Adult↗
PubMed1988

Adriamycin custom-tailored immunoconjugates in the treatment of human malignancies.

Twenty-three patients with disseminated refractory malignancies each received a tailored combination of adriamycin-conjugated murine monoclonal antibodies. Tumors were typed using a panel of antibodies. Cocktails of up to six antibodies were selected based on binding greater than 80% of the malignant cells as tested by immunoperoxidase and flow cytometry. These monoclonal antibodies were then conjugated to Adriamycin and administered intravenously. Seventeen of 23 patients had reactions to the administration of immunoconjugates, but these were tolerable in all but two patients. Fever, chills, pruritus, and skin rash were by far the most common transitory reactions. All were well controlled with premedication. In several patients there was limited antigenic drift among various biopsies within the same patient over time. This observation confirms the necessity for the use of a cocktail of antibodies if one wishes to cover all tumor cells. Preliminary serologic evidence suggests that the development of an IgM antibody, which is specific against the mouse monoclonal antibody, has the specificity and sensitivity to predict clinical reactions. Selected patients were re-treated. One patient with chronic lymphocytic leukemia had re-treatment on three occasions and demonstrated regression of peripheral lymph nodes. Two patients with breast carcinoma had definite improvement in ulcerating skin lesions and two patients with tongue carcinoma had shrinkage of their lesions. In the course of the study free Adriamycin released from the monoclonal antibodies was discovered to be a limiting factor in the amount of antibody that could be administered. Up to 1 g of Adriamycin and up to 5 g of monoclonal antibody were administered. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody that unpredictably caused hemopoietic depression. This study demonstrates the feasibility and reviews technical considerations in preparing immunoconjugate cocktails for patients with refractory malignancies. The major technical hurdle appears to be the selection of an effective conjugation method that can be used to optimally bind Adriamycin to monoclonal antibodies for targeted cancer therapy.

Animals↗
PubMed1987

Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide.

Standard chemotherapy for disseminated germ-cell tumors includes a combination of cisplatin, vinblastine, and bleomycin, but this regimen produces substantial neuromuscular toxicity. In a randomized clinical trial in 261 men with disseminated germ-cell tumors, we substituted etoposide for the vinblastine in this regimen in half the patients to compare the efficacy and toxicity of the two treatments. Among 244 patients who could be evaluated for a response, 74 percent of those receiving the regimen including vinblastine and 83 percent of those receiving the regimen including etoposide became disease-free with or without subsequent surgery (P not significant). Among the 157 patients with high tumor volume, 61 percent became disease-free on the regimen that included vinblastine, as compared with 77 percent on the regimen that included etoposide (P less than 0.05). Survival among the patients who received etoposide was higher (P = 0.048). The regimens were similar in terms of myelosuppressive effects and pulmonary toxicity. However, the etoposide regimen caused substantially fewer paresthesias (P = 0.02), abdominal cramps (P = 0.0008), and myalgias (P = 0.00002). We conclude that etoposide with cisplatin and bleomycin is superior to vinblastine with cisplatin and bleomycin in the treatment of disseminated germ-cell tumors because of diminished neuromuscular toxicity and, among patients with advanced disease, better efficacy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Phase III comparison of cisplatin alone versus cisplatin, doxorubicin and cyclophosphamide in the treatment of bladder (urothelial) cancer: a Southeastern Cancer Study Group trial.

A prospective randomized trial compared cisplatin alone versus cisplatin, doxorubicin and cyclophosphamide in the treatment of advanced carcinoma of the bladder, ureter and renal pelvis. Objective responses were noted in 7 of 45 patients (16 per cent) given cisplatin alone and in 9 of 42 (21 per cent) treated with the combination. There was no significant difference in response rate, response duration or survival but the combination was more toxic. Other combination regimens should be evaluated.

Aged↗
PubMed1987

A randomized comparison of high-dose versus conventional-dose cyclophosphamide, doxorubicin, and vincristine for extensive-stage small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group.

To assess the effect of dose escalation in the treatment of small-cell lung cancer (SCLC), 298 patients with extensive-stage disease were treated with either conventional-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1 mg/m2), (CDCAV); or high-dose cyclophosphamide (1,200 mg/m2), doxorubicin (70 mg/m2), and vincristine (1 mg/m2) (HDCAV). No dose attenuation was allowed during the initial three cycles of therapy in either treatment arm. All patients received CDCAV in cycles 4 through 6, during which time dosages were adjusted according to granulocyte and platelet nadirs. No additional chemotherapy was administered until disease progression or relapse was documented. Complete responses were more frequent with HDCAV (22% v 12%; P = .045). However, overall response rate (63% v 53%) and median survival (29.3 v 34.7 weeks) were not significantly different (P greater than .05). HDCAV was substantially more toxic than CDCAV, causing more episodes of life-threatening leukopenia (ie, granulocytes less than 500/microL; 79% v 40%; P less than .05) and infections (15% v 4%; P less than .05). Dose intensification of cyclophosphamide and doxorubicin during induction chemotherapy did not produce any survival benefit compared with conventional dosages of these agents in SCLC patients with extensive-stage disease.

Adult↗
PubMed1987

Chemotherapy of metastatic seminoma: the Southeastern Cancer Study Group experience.

From 1978 to 1984, 62 patients with advanced seminoma of testicular or extragonadal origin were entered on two consecutive Southeastern Cancer Study Group (SECSG) protocols. All patients had progressive disease and were stratified according to tumor burden. Randomization on SEG 78-GU240 was cisplatin, vinblastine, and bleomycin (PVB), with or without doxorubicin; on SEG 81-GU332, randomization was to PVB or cisplatin, etoposide (VP-16), and bleomycin (PVP16B). Dosages of etoposide, vinblastine, and doxorubicin were decreased by 25% in patients who had received prior radiotherapy. Thirty patients (55%) had received prior chest and/or abdominal radiotherapy. Overall, 41 of 60 evaluable patients (68%) achieved a complete remission (CR) and 37 patients are alive and free of disease. CR was obtained in 13 of 15 patients (87%) with minimal disease, 13 of 16 (81%) with moderate disease, and 15 of 29 (52%) with advanced disease. Patients with no prior radiotherapy or limited-field (chest or abdomen) radiotherapy were more likely to achieve CR than those with prior chest and abdominal radiotherapy (75% v. 42%). Using univariate analysis, the extent of disease is the only significant prognostic factor, whereas both extent of disease and extent of prior radiotherapy are significant in a multivariate analysis. This study confirms the chemosensitivity of metastatic seminoma in a cooperative group setting and defines prognostic factors useful for comparison of other chemotherapeutic trials in seminoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Obesity and serum lipids: an evaluation of the relative contribution of body fat and fat distribution to lipid levels.

The association of obesity and hyperlipidemia does not mean that fatness per se is the primary determinant of the lipid abnormality. To evaluate the contribution of fatness to fasting levels of serum triglycerides (TG), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C), we analyzed data on 368 caucasian adults (286 women, 82 men) consecutively entering a weight control program. Although most subjects were overweight, the population represented a wide spectrum of body weights and lipid levels. Study variables included body fat mass (by total body water), fat free mass (FFM), body build (chest to height ratio), fat cell size and number (from bilateral buttock biopsy specimens), upper-lower body fat pattern by arm to thigh circumference ratio, central-peripheral fat pattern by subcapsular to triceps skinfold ratio, waist to hip ratio, and the presence or absence of diabetes. Our results concurred with previously noted correlations of body weight with TG (r = 0.29, P less than 0.0001) and with HDL-C (r = -0.28, P less than 0.0001) at least in the larger sample of women, but there was no significant correlation with LDL-C (r = -0.06). In order to evaluate the relative contribution of the various components of body composition and fat distribution to lipid levels, stepwise regression analyses were performed on the subgroups of women and men. Among women: TG level was predicted best by FFM, upper body fat pattern, age, and diabetes (explaining 30 percent of TG variance); LDL-C level was predicted by age only (explaining 12 percent of variance); and HDL-C level was predicted by body build only (8 percent). Among men: TG level was predicted best by central and upper body fat patterns and diabetes (31 percent of variance); LDL-C and HDL-C levels were not significantly predicted by any of the 11 study variables. These results, obtained from cross-sectional analysis of a predominantly obese sample, suggest that lipid levels may be more directly related to body fat pattern, fat free mass and body build than to body fatness itself.

Adipose Tissue↗