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Biomedical subjects

R Makuch

Publications and source records attributed to R Makuch.

62 records · Page 4Linked to original sources
PubMed1979

Cyclic alternating combination chemotherapy for small cell bronchogenic carcinoma.

Sixty-one protocol-eligible patients with small cell bronchogenic carcinoma received cyclic alternating combination chemotherapy with two or three non-cross-resistant drug combinations. No chest or prophylactic brain radiation therapy was used. Twenty-eight months after starting treatment, disease-free survival was 23% for patients achieving a complete response (CR) and 13% overall. Initial treatment consisted of high-dose cyclophosphamide, methotrexate, and CCNU (CMC) for 6 weeks. Patients then received vincristine, adriamycin, and procarbazine (VAP) for 6 weeks. The addition of VAP increased the CR rate from 42% to 74% in limited-disease patients and from 24% to 36% in extensive-disease patients. Half of the patients were randomized to a third combination of VO-16-213 and ifosfamide. These patients were cycled at 6-week intervals through the three drug regimens while the remaining patients were cycled between CMC and VAP. The addition of VP-16-213 and ifosfamide did not increase the CR rate or prolong survival. Only complete responders survived beyond 24 months. Sequential use of non-cross-resistant drug combinations represents one method for increasing the CR rate.

Antineoplastic Agents↗
PubMed1978

Thymosin in cancer patients: in vitro effects and correlations with clinical response to thymosin immunotherapy.

Studies on the effect of thymosin on T-cell levels in vitro among normal persons and cancer patients show that, in general, T-cell levels increase after incubation with thymosin in populations with low initial T-cell levels while the levels decrease in populations with high initial T-cell levels. In patients with small cell carcinoma of the lung receiving intensive chemotherapy also randomized to receive thymosin at a dose of 60 mg/m2, thymosin at a dose of 20 mg/m2, or placebo twice weekly, increased survival occurred in patients receiving the thymosin dose of 60 mg/m2. The increase in survival was greatest in patients with low pretreatment T-cell and alpha2HS-glycoprotein levels. These observations suggest that the cancer patients most likely to benefit therapeutically from adjuvant treatment with thymosin are those with relatively low initial T-cell levels and other parameters of cellular immunity.

Carcinoma, Small Cell↗
PubMed1978

Sample size requirements for evaluating a conservative therapy.

Determination of an adequate sample size for a clinical trial has traditionally involved the specification of type I (false positive) and type II (false negative) error rates, and a difference that one wishes to detect. Because newer therapy has generally been more invasive or more toxic, it is conventional for the type I error to be 0.05 in order that new therapy not be accepted as superior unless its advantages are definitively established. Recently, many new trials have been directed toward showing that a more conservative treatment is equivalent in efficacy to a standard intensive therapy. In this paper, we provide formulas which prescribe the sample size necessary to meet certain criteria specified by the investigator for this alternative type of clinical trial. In addition, the percent increase in total sample size is described when more patients are allocated to one treatment than the other.

Biometry↗
PubMedDate not supplied

Early detection of ovarian cancer: background, rationale, and structure of the Yale Early Detection Program.

Ovarian cancer has received national attention as a highly virulent disease. Its lack of early warning symptoms and the failure to develop highly sensitive screening tests have led some physicians to recommend prophylactic oophorectomies to women with relatives who have had ovarian cancer. Others have recommended routine screening of otherwise normal women for CA 125, a circulating tumor marker, and ultrasound examinations. Each of these techniques is associated with substantial false-positive rates that could lead to unnecessary surgery. A review of epidemiologic data suggests that familial ovarian cancer kindreds are rare, but women with first-degree relatives who have had ovarian cancer have a significant risk themselves for developing ovarian cancer. In addition, women with a great number of ovulatory cycles are at an increased risk for the disease. Circulating tumor markers are frequently elevated in women with advanced ovarian cancer, but their value in early detection of ovarian cancer has yet to be established. Advances in endovaginal ultrasound and color Doppler flow technology have significantly improved our ability to assess pelvic organs. This article presents the background, rationale, and structure of the Yale Early Detection Program for ovarian cancer, whose goals are to identify the best techniques for diagnosing ovarian cancer in an early stage, to determine the frequency with which such tests should be employed, to assess false-positive results, and to identify women who might benefit from prophylactic oophorectomies.

Biomarkers, Tumor↗
PubMedDate not supplied

Early detection of ovarian cancer: preliminary results of the Yale Early Detection Program.

Eighty-four women at high risk for ovarian cancer by having first-degree relatives with epithelial ovarian cancer participated in a newly established, early ovarian cancer detection program at Yale University. Participants were to be evaluated with physical examinations and circulating tumor markers at entry and every six months thereafter. Endovaginal ultrasound and color Doppler flow studies were to be performed at three and nine months following entry into the program. In addition, women were encouraged to follow American Cancer Society guidelines for mammography. Stool was checked for occult blood. Endometrial sampling was offered to post-menopausal women. No participant has developed an ovarian cancer since entering the program. One woman has been diagnosed to have breast cancer. False-positive levels of circulating tumor markers (CA 125, 4/84 [4.8 percent]; lipid-associated sialic acid in plasma, 13/84 [15.5 percent]; NB/70K, 4/84 [4.8 percent]; and urinary gonadotropin fragment, 1/65 [1.5 percent]) were observed on entry into the program. Low resistive indices (less than 0.5) were documented in 8/91 (8.8 percent) ovaries studied by the color Doppler flow technique. One participant underwent a laparotomy based on a false-positive endovaginal ultrasound examination. Tests now being employed in community practice have a high likelihood of being associated with false-positive results. Therapeutic interventions based on isolated abnormal tumor markers or ultrasound studies obtained from women with family histories of ovarian cancer may lead to inappropriate surgery. It is necessary for cancer centers to develop expertise in ovarian cancer detection techniques to advise physicians in their geographic areas appropriately about the significance of the abnormal screening test.

Adult↗
PubMedDate not supplied

cis-Dichlorodiammineplatinum(II) for the treatment of advanced ovarian cancer.

cis-Dichlorodiammineplatinum(II) (cis-platinum) was used in the treatment of 25 patients with advanced ovarian adenocarcinoma refractory to alkylating agents. Seven of 24 evaluable patients (29%) responded to cis-platinum (one complete response and six partial responses). Life-table analysis of survival indicates that patients responding to therapy survive longer than those who fail to respond (9 months versus 3.2 months) (P = 0.014). In previously treated patients given 70 mg/m2 iv with forced diuresis, there was substantial nausea and vomiting (100%), hematologic toxicity (67%), and renal toxicity (34%). A review of the single-agent activity of cis-platinum in other ovarian cancer studies indicates an overall response rate of 25% (40 of 161 patients). At least nine combination chemotherapy studies utilizing cis-platinum are in progress, and preliminary information from several of these is encouraging and suggests that cis-platinum-containing combinations may have a major role in the treatment of ovarian adenocarcinoma.

Adenocarcinoma↗
PubMedDate not supplied

Laboratory parameters as an alternative to performance status in prognostic stratification of patients with small cell lung cancer.

Pretreatment performance status (PS)is a major prognostic factor for both treatment response and survival duration in cancer clinical trials. PS is, however, a subjective index that may be markedly influenced by acute self-limited events. The objective of this study was to develop a prognostic index, based on pretreatment laboratory results, that might serve as an alternative to PS in patients with small cell anaplastic lung cancer. Results have been analyzed in 56 newly diagnosed patients with a minimum followup of 10 months and a median followup of 21 months. Patients were divided into high and low groups for each laboratory parameter based on readings either above or below the median value. Patients with high hemoglobin or albumin levels or low serum alpha-1 globulins, gamma globulins, or LDH survived significantly longer than patients with the opposite levels. When these factors were evaluated by multivariate analysis, albumin and hemoglobin were the most influential prognostic factors for survival. After inclusion of these two laboratory parameters, PS was no longer a significant prognosticator of survival. An objective prognostic index based on pretreatment laboratory results appears feasible in patients with small cell lung cancer.

Carcinoma, Small Cell↗