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Biomedical subjects

K J Propert

Publications and source records attributed to K J Propert.

51 records · Page 3Linked to original sources
PubMed1989

A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B.

The Cancer and Leukemia Group B (CALGB) conducted a prospective randomized trial to evaluate the role of warfarin and alternating chemotherapy in extensive small-cell lung cancer (SCCL). After stratification for sex and performance status, patients were randomly assigned to receive chemotherapy with methotrexate, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (CCNU) (MACC), or MACC plus warfarin (MACC + W), or mitomycin, etoposide, cisplatin, and hexamethylmelamine alternating with MACC (MEPH/MACC). Warfarin was given continuously to maintain a prothrombin time of one and one half to twice the control values. A total of 328 patients were enrolled, and 294 were evaluable. There was a statistically significant advantage in objective response rates (complete [CR] and partial responses [PR], respectively) for MACC + W (17% and 50%) as compared with MACC alone (8% and 43%) or MEPH/MACC (10% and 38%) (P = .012). Both failure-free survival (P = .054 Wilcoxon test) and overall survival (P = .098 Wilcoxon test) were higher on MACC + W (median, 6.6 months and 9.3 months, respectively), as compared with MACC (5.0 months and 7.9 months) and MEPH/MACC (5.0 months and 7.9 months). Toxicity was comparable among the three arms, except for increased hemorrhagic events on MACC + W, which were life-threatening in four patients (4%), and lethal in two others (2%). These data support the role of warfarin in the treatment of SCCL, but do not establish its mechanism of action. Warfarin deserves further studies in SCCL, particularly in patients with limited disease.

Altretamine↗
PubMed1988

Phase II trial of 4'-deoxydoxorubicin (DxDx) in non-small cell lung cancer: a Cancer and Leukemia Group B Trial.

Eighty-seven patients with histologically or cytologically proven non-small-cell carcinoma of the lung were treated with 4'-deoxydoxorubicin (DxDx) 30 mg/m2 every 3 weeks. Three responses (4%), all partial, were observed. All responses occurred in patients with large-cell anaplastic lung cancer and none in squamous or adenocarcinoma histologies (P less than 0.01). The durations of partial response for these three responders were 70, 198+ and 209+ days. The side effects noted were predominantly neutropenia, anemia, and weight loss. In three patients, declines in cardiac ejection fraction of 7%, 12%, and 23% occurred after cumulative drug doses of 150 mg/m2, 150 mg/m2, and 233 mg/m2, respectively. 4'-Deoxydoxorubicin had little activity in non-small-cell lung cancer at the dose used in this study.

Carcinoma, Non-Small-Cell Lung↗
PubMed1988

Assessing the effect of toxicity on prognosis: methods of analysis and interpretation.

There has recently been an increased interest in and reporting of the association between toxicity and treatment outcome in cancer clinical trials. Such comparisons may be used to suggest mechanisms by which cytotoxic agents function in the cancer patient, especially regarding the importance of the effect of dose on the individual patient. However, analyses of "time-to-failure" outcomes such as survival by toxicity are subject to bias due to the time-dependence of both the predictor and outcome variables. In addition, interpretation of even appropriately conducted statistical analyses is problematic, as with analyses of survival by outcome variables such as response. The use of statistical methodology designed to avoid such biases in these comparisons is shown and the problems in the interpretation of results are discussed.

Antineoplastic Agents↗
PubMed1987

Chemotherapy with or without radiation therapy in limited small-cell carcinoma of the lung.

We conducted a prospective, randomized study to clarify the role of radiotherapy of the primary tumor in limited small-cell cancer of the lung. After stratification for sex and for performance score based on the ability to ambulate, patients were randomly assigned to receive initial radiotherapy plus chemotherapy, delayed radiotherapy plus chemotherapy, or chemotherapy alone. The chemotherapy consisted of cyclophosphamide, etoposide (VP-16-213), and vincristine, with doxorubicin subsequently replacing etoposide in alternate cycles 7 through 18. Chemotherapy was given every three weeks for 18 months. The radiotherapy comprised 4000 rad in four weeks, followed by a 1000-rad "boost" directed against residual disease. All patients received prophylactic whole-brain radiation. The patients enrolled totaled 426, and 399 were evaluable. There was a statistically significant difference in the frequency of complete responses in favor of the two radiotherapy regimens (P = 0.0013). Failure-free survival was also longer with these two regimens (P less than 0.001), as was the interval before treatment failure in the chest (P less than 0.001) and overall survival (P = 0.0099). As expected, toxic effects--chiefly neutropenia--were also increased. The addition of radiotherapy of the primary tumor to combination chemotherapy improved both complete-response rates and survival, with increased but acceptable toxicity.

Aged↗
PubMed1987

A phase II trial of cyclophosphamide, etoposide, and cisplatin with combined chest and brain radiotherapy in limited small-cell lung cancer: a Cancer and Leukemia Group B Study.

Limited-extent small-cell lung carcinoma (SCLC) remains a therapeutic problem with little improvement in complete response (CR) rates and long-term survival in the past 5 years. From June 1984 through January 1985, 56 patients with limited-extent SCLC were enrolled in a Cancer and Leukemia Group B (CALGB) phase II study using five cycles of cyclophosphamide (500 mg/m2 intravenously [IV] day 1), etoposide (80 mg/m2 IV days 1 to 3), and cisplatin (33 mg/m2 IV days 1 to 3) administered at 3-week intervals (CEP), with radiation therapy (50 Gy to chest and 30 Gy to brain) administered concomitant with cycles 4 and 5, followed by three cycles of cyclophosphamide (500 mg/m2 IV day 1), etoposide (80 mg/m2 IV days 1 to 3), and doxorubicin (50 mg/m2 IV day 1). Of 49 patients evaluable for response, the overall response rate was 88%, with 57% CRs. The median overall survival was 14 months; the median duration of CR was 10 months, and nine CRs remain disease free at a median follow-up of 23 months. Toxicity was significant: 56% patients experienced WBC less than 1,000 microL, 32% platelets less than 25,000 microL and 10% hemoglobin less than 7 g/dL. There was one treatment-related septic death. These results are as good as the best previous CALGB study of SCLC, despite a reduction in duration of treatment from 18 to 5 months. We are currently using a variant of this multimodality treatment approach as our standard management for patients with limited-extent SCLC.

Adult↗
PubMed1987

Carboplatin or iproplatin in advanced non-small cell lung cancer: a Cancer and Leukemia Group B Study.

The effect of the cisplatin analogs carboplatin (CBDCA) or iproplatin (CHIP) was evaluated in patients with extensive non-small cell lung cancer. The randomized phase II design was used to achieve balance between patient groups and comparison of response rates was not a primary objective of the study. CBDCA (400 mg/m2 iv) or CHIP (270 mg/m2 iv) was administered every 4 weeks until relapse of disease. Overall, 11 of 70 patients (16%; 95% confidence interval: 7%-25%) responded to CBDCA and five of 71 patients (7%; 95% confidence interval: 1%-13%) responded to CHIP. There were two complete responses to CHIP and none to CBDCA. The most frequent severe or life-threatening toxic effects were thrombocytopenia and leukopenia. Median survival for patients receiving CBDCA was 6.5 months; for those on CHIP it was 5.0 months (P = 0.59). CBDCA is probably active in patients with non-small cell lung cancer whereas CHIP has limited activity. Further evaluation of CBDCA as part of combination chemotherapy for non-small cell lung cancer is warranted.

Adult↗
PubMed1986

Alternating cycles of combination chemotherapy for patients with recurrent Hodgkin's disease following radiotherapy. A prospectively randomized study by the Cancer and Leukemia Group B.

A randomized clinical trial of combination chemotherapy for patients who relapsed following primary radiation therapy for Hodgkin's disease was conducted from 1975 to 1981 by the Cancer and Leukemia Group B (CALGB). One hundred thirteen patients were prospectively randomized to receive 12 cycles of either CVPP (CCNU, vinblastine, procarbazine, and prednisone), ABOS (bleomycin, vincristine [Oncovin; Lilly, Indianapolis], doxorubicin [Adriamycin, Adria Laboratories, Columbus, Ohio], and streptozotocin), or alternating cycles of CVPP and ABOS. The median length of observation for patients in this report is 4 years. Toxicities of the three treatment programs were primarily hematologic. Frequencies of complete response were 72% for CVPP, 70% for ABOS, and 82% for CVPP/ABOS (P = .37). Females and patients who had nodular sclerosing disease at initial diagnosis had significantly higher complete response rates. The 5-year disease-free survival for the complete responders was 55%; the 5-year overall survival was 60%. There were no significant differences among the treatments on disease-free survival (P = .78) or overall survival (P = .18). Age under 40 years was the only significant positive prognostic factor for disease-free survival (P = .095) and overall survival (P = .003). This study demonstrates no statistically significant advantage for alternating cycles of combination chemotherapy in affecting complete response frequency, disease-free survival, or overall survival as compared with therapy with CVPP or ABOS alone. However, the power to detect differences in these outcome parameters is somewhat limited by the sample sizes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Single, sequential, and multiple alkylating agent therapy for multiple myeloma: a CALGB Study.

Four intravenous (IV) alkylating agent regimens were tested in 615 previously untreated patients with multiple myeloma. Patients were randomized to receive melphalan, cyclophosphamide, and carmustine in combination (MCBP), sequentially (Seq-MCBP), or in combination with doxorubicin (MCBPA). The fourth group received IV melphalan (MP) as the only alkylating agent. All groups received a tapering dose of prednisone. Toxicity was similar for all regimens although the nadir of cytopenia was reached more quickly for the regime including melphalan only. Response as measured by reduction in myeloma protein or other parameters were similar for the four treatments. Survival was significantly poorer for the group receiving the alkylating agents in sequence. The survival of high tumor cell load patients who were azotemic was better in the groups treated with IV MP or with the combination of IV MCBP. In view of the simplicity and probable cost savings attached to single-agent treatment, a melphalan/prednisone regimen should be considered as initial therapy for all patients with myeloma.

Adult↗
PubMed1982

Early maternal behaviors predictive of the survival of suckling rats with intergenerational malnutrition.

Mother-pup interactions during the first 12 hours post partum were studied in intergenerationally malnourished and control rats. Pup mortality during the suckling period was found to be associated with nutritional status with only 50% survival in the malnourished series, as compared to 100% survival in the control series. Litters with subsequent high pup mortality were distinguished by abnormal mothering patterns during the first 12 hours of life and reduced pup weight at the end of this period. High pup mortality was associated with increased active nursing, and reductions in passive nursing, pup licking, amount of contact with the pups and time spent in the nest by the lactating female. Thus, the stimulus to active nursing is most intense under conditions where the pups are least likely to survive, whereas the amount of stimulation provided to such pups is reduced. Maximal associations between early mother-pup interactions and subsequent pup weight and survival were present 7-9 hours after birth.

Animal Population Groups↗
PubMed1981

Maternal behavior following rehabilitation of rats with intergenerational malnutrition. 1. Persistent changes in lactation-related behaviors.

Female rats rehabilitated for one or two generations on an adequate level of dietary protein following a history of intergenerational malnutrition were studied during the postnatal suckling period. No recovery occurred after two generations of dietary rehabilitation for most measures of maternal behavior including active nursing, passive nursing, pup-oriented behavior, time spent in the nest or time spent in contact with the young. In contrast, nest quality improved to normal levels after rehabilitation. In addition, growth of pups born to females rehabilitated for one generation was similar to growth of control pups, and in the case of mothers rehabilitated for two generations, growth of offspring exceeded that of the control pups. These results demonstrate variable sensitivity of different maternal behaviors to rehabilitation following a history of intergenerational malnutrition, with lack of normalization of a considerable number of maternal behaviors. Consequently, some of these abnormalities in maternal behavior may result in persistent abnormalities in the behavior of offspring over several generations.

Age Factors↗
PubMed1981

Maternal behavior following rehabilitation of rats with intergenerational malnutrition. 2. Contribution of mothers and pups to deficits in lactation-related behaviors.

In a companion paper, we reported the persistence of an increase in active nursing and nursing-related behaviors in rats that were rehabilitated following prolonged intergenerational malnutrition. The rehabilitated litters contained females and pups fed an adequate diet for up to three generations after a history of malnutrition. In the current study, a 2 X 2 cross-over design was used during the lactation period in which rehabilitated mothers suckled rehabilitated pups or well-nourished control pups, and control mothers similarly suckled rehabilitated or control pups. We found that maternal factors were dominant in determining the amount of active nursing, and that pup factors modified the maternal influence on other lactation-related behaviors.

Animals↗