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Biomedical subjects

M C Perry

Publications and source records attributed to M C Perry.

At least 19 recordsLinked to original sources
PubMed1997

Phase I trial of etoposide, carboplatin, and GM-CSF in extensive small-cell lung cancer: a Cancer and Leukemia Group B study (CALGB 8832).

The maximum tolerated dose (MTD) of etoposide and carboplatin without growth factor support was previously defined by Cancer and Leukemia Group B (CALGB) as 200 and 125 mg/m2/day x 3, respectively, given every 28 days to previously untreated patients who have extensive, small-cell lung cancer (SCLC). Myelosuppression was dose-limiting. The purpose of this phase I trial was to determine if granulocyte macrophage colony-stimulating factor (GM-CSF) support allows the dosage of the combination of etoposide and carboplatin to be increased above the previously determined MTD. In this CALGB study of 44 evaluable patients with performance status 0-2, cohorts were treated with etoposide and carboplatin given intravenously on days 1-3 followed by GM-CSF (molgramostim) given subcutaneously on days 4-18. Four dose levels of bacteria-derived recombinant GM-CSF (5, 10, 20 microg/kg/day and 5 microg/kg every 12 h), three dose levels of etoposide (200, 250, and 300 mg/m2/day x 3), and two dose levels of carboplatin (125 and 150 mg/m2/day x 3) were evaluated. There was no chemotherapy dose escalation in individual patients. With 5 microg/kg/d GM-CSF, the first etoposide and carboplatin cycle of 300 and 150 mg/m2/day x 3, respectively, could be administered with acceptable toxicity. However, GM-CSF did not allow repeated administration of this dose-escalated regimen every 21 days, since delayed platelet and/or neutrophil recovery was dose limiting in later cycles. These results demonstrate that GM-CSF alone has limited capability to support the repeated administration of high doses of etoposide and carboplatin. CALGB currently is testing the ability of interleukin (IL)-6 given with GM-CSF to ameliorate the cumulative myelosuppression of this intense regimen.

Adult↗
PubMed1997

Future directions in the therapy of small cell lung cancer.

Current therapy for small cell lung cancer seems to have reached a plateau. To rise off this plateau it will be necessary to improve local control through radiation therapy, and control of distant metastases with new chemotherapy strategies. It will also be necessary to treat pharmacologic sanctuaries, reduce treatment-related toxicities, and prevent second malignancies.

Algorithms↗
PubMed1996

A phase I/II trial of etoposide and cisplatin in extensive small cell lung cancer: a cancer and leukemia group B study.

Patients with untreated extensive small cell lung cancer (SCLC) with CALGB performance scores 0-2 were treated with etoposide 200 mg/m2/day on days 1-3 and cisplatin doses of 20, 30, or 35 mg/m2/day days 1-3 in a Phase I/II format. Of the nine patients treated at the 35 mg/m2/day cisplatin dose in the Phase I portion of the study, Grade 4 leukopenia occurred in five patients and Grade 4 thrombocytopenia in four. There were two deaths due to myelosuppression and sepsis. This dose was thus considered the maximum tolerated dose (MTD), and a Phase II trial was then conducted using this treatment program. In the Phase II trial of 39 patients, the objective response rate was 67% (95% confidence interval, 50-81%) with 21% complete responses (CI 9-36%). Median survival was 10.5 months. Grade 4-5 leukopenia was seen in 57% and Grade 4-5 thrombocytopenia in 56%. The MTD defined by this Phase I trial represents a 67-100% increase in etoposide and a 32-42% increase in cisplatin dosage compared to prior studies. The observed objective response rates with this regimen are comparable to studies using conventional doses, but hematological toxicity was higher.

Adult↗
PubMed1996

Postsurgical adjuvant chemotherapy of stage II breast carcinoma with or without crossover to a non-cross-resistant regimen: a Cancer and Leukemia Group B study.

PURPOSE: To compare two cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) regimens with a doxorubicin-based regimen--vinblastine, doxorubicin, thiotepa, and Halotestin (Upjohn, Kalamazoo, MI) (VATH)--in patients with stage II node-positive breast carcinoma. METHODS: Nine hundred forty-five women were treated with a 6-week induction course of CMFVP. They were then randomized to receive one of two consolidation CMFVP regimens: 6-week courses or 2-week courses. Following completion of CMFVP consolidation, patients were again randomized to either continue the CMFVP regimen or to receive six escalating doses of VATH. RESULTS: Among all patients, with a median follow-up time of 11.5 years, there is no statistically significant difference in disease-free survival (DFS) between the two consolidation CMFVP regimens. VATH intensification treatment is statistically significantly superior to CMFVP in terms of DFS (P = .0040). For patients with one to three involved nodes, there is currently no significant difference between VATH and CMFVP; however, among those with four or more positive lymph nodes, there is a significant difference in favor of VATH (P = .0037). There is also improved overall survival with VATH (P = .043; median, > 14 years v 10 years). This difference is also statistically significant in patients with four or more involved lymph nodes, among postmenopausal patients, and among postmenopausal estrogen receptor-positive patients. CONCLUSION: Chemotherapy with crossover to escalating doses of VATH following CMFVP was well tolerated and effective. Inauguration of VATH as a treatment intensification at the eighth month produced a major increase in relapse-free and overall survival. The observation that sensitivity to VATH is retained so long after mastectomy raises questions about the proper duration of adjuvant chemotherapy and lends support to further investigation of cross-over designs in future trials to postoperative adjuvant chemotherapy regimens.

Adult↗
PubMed1996

REACH: an alternative early return to work program.

One of the most frequently cited strategies for successful return to work post-injury or illness--early return to work--is often an unattainable goal for many employees. Returning injured or ill employees to an existing program outside of the company (where the injury or illness occurred) is a means of overcoming the obstacles often associated with early return to work programs. A significant reduction in workers' compensation costs was demonstrated for employees participating in the early return to work program that placed ill or injured workers in positions at workshops for the developmentally disabled. This reduction in costs was demonstrated while paying these employees 100% of their wages rather than the lesser compensation amount.

Cost Savings↗
PubMed1996

The multiple sleep latency test: comparison of sleep onset criteria.

Determining sleep latency is one of the cornerstones of the interpretation of the multiple sleep latency test (MSLT). The purpose of this study was to compare various criteria used to determine sleep onset. We prospectively analyzed 100 consecutive MSLTs that were performed according to a standardized protocol. We scored each test using three separate sets of criteria for sleep onset: 1) one epoch of stage 1 sleep, 2) two consecutive epochs of stage 1 sleep, and 3) three consecutive epochs of stage 1 sleep. Each method yielded a mean sleep latency and a categorical classification of the record as normal if > 10 minutes, moderate if > or = 5 and < or = 10 minutes, and severe sleepiness if < 5 minutes. The ages of participants ranged from 4 to 78 years (mean 45.5). The averages of the mean sleep latencies across all three methods were: 6.2 minutes [standard deviation (SD) = 4.3] using one epoch, 7.2 minutes (SD = 4.7) using two epochs, and 7.5 minutes (SD = 4.9) using three epochs. Using the three categories of sleepiness, the implementation of the three-epoch criterion vs. the one-epoch criterion produced a change in category in 16 patients (16%). Five went from severe to moderate, 10 from moderate to normal, and 1 from severe to normal. As compared to using one epoch, using three produced an increase in mean sleep latency of at least 50% in 13 patients. The use of various criteria for sleep onset, especially criteria 1 and 3 above, produces differences in interpretation that are neither rare nor quantitatively negligible. Standardization of the methodology across centers would be desirable in clinical practice as well as for research protocols.

Adolescent↗
PubMed1995

Alternating chemotherapy regimens for patients with metastatic breast cancer. A pilot study based on tumor marker kinetics. Cancer and Leukemia Group B.

BACKGROUND: Chemotherapy is most effective when applied during the biologically active stage of tumor cells. According to the authors' previous tumor marker kinetic study, methotrexate plus 5-fluorouracil (MF) was found to yield either a cytolytic effect in an MF-sensitive tumor cell population or a cytostatic effect in an MF-resistant population. In the latter, the suppressive effect was transient and the biologic activity resumed in one week after MF administration. METHODS: Based on this marker kinetic study, an alternating chemotherapy program was designed to study its antitumor and side effects. Methotrexate (M) (200 mg/m2) and 5-fluorouracil (F) (500 mg/m2) were administered intravenously on day 1 followed 24 hours later by leucovorin (L) (10 mg/m2 orally every 6 hours for 6 doses). Cyclophosphamide (C) 300 (mg/m2), doxorubicin (A) (50 mg/m2), and vincristine (V) (1 mg/m2) were given on day 8. The MFL/CAV was given every 4 weeks. RESULTS: Forty-nine patients with metastatic breast cancer were enrolled; 41 were eligible. There were 5 complete and 23 partial remissions, producing a total response rate of 68%. In 15 patients with liver metastases, the response rate was 73% and the median survival 13.7 months, results superior to those previously reported for this subgroup of patients. Side effects were manageable. CONCLUSIONS: This regimen, which can be given safely in an outpatient setting, yielded encouraging response and survival rates in patients with visceral-dominant disease with poor prognoses.

Adult↗
PubMed1995

Interrater reliability of the multiple sleep latency test.

The purpose of this study was to evaluate interrater reliability in the interpretation of the multiple sleep latency test (MSLT). We prospectively analyzed MSLTs performed on 21 patients with excessive daytime sleepiness. MSLTs were recorded on Grass Model 78 polygraphs with EEG, electro-oculogram, and chin EMG. Each test was performed simultaneously at paper speeds of 10 and 30 mm/sec and was scored blindly by 3 readers using standard criteria. For the quantitative variable (sleep latency), a LISREL model was used. For the binary variable (REM present or not), a kappa coefficient was used. Interrater reliability of sleep latency was 0.850 at speed 10, and 0.884 at speed 30. There was no significant difference between speed 10 and 30. Interrater reliability for the presence or absence of REM was 0.515-0.563 at speed 10, and 0.447-0.525 at speed 30. On the MSLT, the estimation of sleep latency showed excellent consistency between different readers. The determination of the presence or absence of REM only showed fair to good agreement among observers. There was no significant difference between a paper speed of 10 vs. 30 mm/sec.

Adolescent↗
PubMed1995

Etoposide (VP-16) and cisplatin at maximum tolerated dose in non-small cell lung carcinoma: a Cancer and Leukemia Group B study.

A multi-institutional cooperative group trial was undertaken by the Cancer and Leukemia Group B (CALGB) to evaluate the efficacy of the combination of cisplatin and intravenous etoposide for the treatment of metastatic or recurrent non-small cell lung cancer (NSCLC). The doses used were those previously determined to be the maximally tolerated dose of this drug combination. Forty patients were entered into the trial, 37 of whom were eligible for evaluation. Cisplatin (35 mg/M2/day for 3 days) and etoposide (200 mg/M2/day for 3 days) were administered every 28 days for a planned 6 cycles of therapy. Sixteen of 37 evaluable patients (43%) responded to therapy. Myelosuppression was the dominant toxicity, with 89% of the patients experiencing grade 4 neutropenia, and nearly half grade 3 or 4 thrombocytopenia. Median survival was 8.5 months, with 30% of the patients alive at 1 year and 10% alive at 2 years. Malaise, fatigue, and peripheral neuropathy were the other major toxicities. The combination of etoposide at the dose of 200 mg/M2/day for 3 days and cisplatin at 35 mg/M2/day for 3 days is a highly potent combination against metastatic non-small cell carcinoma.

Adult↗
PubMed1995

Dreams and rapid eye movement sleep in the multiple sleep latency test.

Dreams are closely associated with rapid eye movement (REM) sleep. The purpose of this study was to evaluate the reliability of dreams in predicting the presence of REM sleep during naps of the multiple sleep latency test (MSLT). We prospectively analyzed MSLTs performed in the evaluation of 44 patients with excessive daytime sleepiness. A total of 167 naps were studied. The patients' ages ranged from 11 to 69 years (mean 45 years). There were 26 males and 18 females. The relationship between the presence of reported dreams and the presence of REM sleep was as follows: sensitivity (percentage of naps with REM in which dreams were reported), 59%; specificity (percentage of naps without REM in which no dreams were reported), 63%; positive predictive value (probability that REM occurred if dreaming is present), 29%; and negative predictive value (probability that REM did not occur when no dreaming is present), 85%. In the daytime naps of the MSLT, the presence of reported dreaming did not appear to be a reliable indicator of the presence of REM sleep in the preceding nap.

Adolescent↗
PubMed1995

Hepatotoxicity of chemotherapeutic and oncologic agents.

Problems arise in cancer chemotherapy when liver function tests are not normal, when drugs that possess known hepatic toxicity are to be given, and when abnormalities arise after drug administration. Most hepatotoxic drug reactions are idiosyncratic, occuring because of either hypersensitivity mechanisms or host metabolic idiosyncrasy. The clinician must always consider that liver injury is due to an idiosyncratic drug reaction, especially in a setting where patients typically receive many drugs, such as an oncology service. Chemotherapeutic agents often possess predictable, dose-dependent ("direct") hepatotoxicity, however. This article addresses the spectrum of hepatotoxic effects of chemotherapeutic agents. The hepatotoxic potential of single-agent as well as combination chemotherapy is discussed and recommendations for dose modifications in patients with impaired hepatic function are provided.

Antineoplastic Agents↗
PubMed1994

Studies on signal transduction mechanisms for adrenaline-driven lipolysis in white and brown adipocytes.

White and brown rat adipocytes have been permeabilised by repeated exposure of the cells in suspension to high voltage electrical discharges. The resulting preparations were permeable to low molecular weight materials, e.g., cyclic AMP, propidium iodide, and were stable in suspension with little evidence of rapid resealing, or of gross damage to the cell membrane. Leakage of lactate dehydrogenase was not markedly enhanced except at voltages in excess of 2 kV cm-1 for brown adipocytes. Exogenously-added cyclic AMP stimulated lipolysis (measured as glycerol release) in the electropermeabilised adipocytes far more effectively than in intact adipocytes. In brown, but not in white, adipocytes this effect was enhanced by addition of millimolar ATP. The EC50 for stimulation of glycerol release by cyclic AMP was 0.2 microM in electropermeabilised brown adipocytes, and 2 microM and 40 microM in electropermeabilised white adipocytes obtained from weanling and adult rats respectively. The effect of cyclic AMP on lipolysis was enhanced by addition of an inhibitor of cyclic AMP phosphodiesterases and was reduced by addition of 5'-AMP, adenosine or inosine (in brown adipocytes). Addition of adenosine deaminase caused a small, but significant, enhancement of cyclic AMP-driven lipolysis. Catecholamine-driven lipolysis was observed in electropermeabilised brown and white adipocytes, especially in the presence of GTP. Adrenaline-, and to a lesser extent cyclic AMP-, driven lipolysis in electropermeabilised white adipocytes was inhibited by insulin. This effect of insulin was not enhanced by addition of GTP or of a metabolically stable GTP analogue. The results obtained establish the electropermeabilised preparation as suitable for analysis of signal transduction pathways in white and brown adipocytes.

Adipose Tissue↗
PubMed1994

Quality of life in patients with limited small-cell carcinoma of the lung receiving chemotherapy with or without radiation therapy, for cancer and leukemia group B.

Quality of life was assessed in 57 patients with limited small-cell carcinoma of the lung utilizing psychological scales that measured mood, functional status, and cognitive impairment. These patients received chemotherapy with or without radiotherapy to the primary tumor. All patients received prophylactic cranial radiation. Patients who received the combination of chemotherapy and radiotherapy to both the primary tumor and CNS had an increase in overall survival. However, because of the increased toxicity experienced by these patients, a decrease in quality of life was documented by measures of psychological distress when compared to patients receiving chemotherapy alone. The findings support the importance of utilizing quality of life measures in addition to measures of physical toxicity so that patients can make an informed choice regarding treatment options.

Activities of Daily Living↗