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Biomedical subjects

Michael C Perry

Publications and source records attributed to Michael C Perry.

25 records · Page 2Linked to original sources

Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431.

PURPOSE: To evaluate new drugs in combination with cisplatin in unresectable stage III non-small-cell lung cancer, Cancer and Leukemia Group B (CALGB) conducted a randomized phase II study of two cycles of induction chemotherapy followed by two additional cycles of the same drugs with concomitant radiotherapy. PATIENTS AND METHODS: Eligible patients received four cycles of cisplatin at 80 mg/m(2) on days 1, 22, 43, and 64 with arm 1: gemcitabine 1,250 mg/m(2) on days 1, 8, 22, and 29 and 600 mg/m(2) on days 43, 50, 64, and 71; arm 2: paclitaxel 225 mg/m(2) for 3 hours on days 1 and 22 and 135 mg/m(2) on days 43 and 64; and arm 3: vinorelbine 25 mg/m(2) on days 1, 8, 15, 22, and 29 and 15 mg/m(2) on days 43, 50, 64, and 71. Radiotherapy was initiated on day 43 at 2 Gy/d (total dose, 66 Gy). RESULTS: One hundred seventy-five eligible patients were analyzed. Toxicities during induction chemotherapy consisted primarily of grade 3 or 4 granulocytopenia. Grade 3 or 4 toxicities during concomitant chemoradiotherapy consisted of thrombocytopenia, granulo-cytopenia, and esophagitis. Response rates after completion of radiotherapy were 74%, 67%, and 73% for arms 1, 2, and 3, respectively. Median survival for all patients was 17 months. One-, 2-, and 3-year survival rates for the patients on the three arms were 68%/37%/28%, 62%/29%/19%, and 65%/40%/23%. CONCLUSION: Four cycles of gemcitabine, vinorelbine, or paclitaxel in combination with cisplatin can be administered at these doses and schedules. The observed survival rates exceed those of previous CALGB trials and may be attributable to the use of concomitant chemoradiotherapy. Induction chemotherapy added to concomitant chemoradiotherapy is being evaluated in a phase III randomized trial.

Adult↗

Outcomes among African-American/non-African-American patients with advanced non-small-cell lung carcinoma: report from the Cancer and Leukemia Group B.

BACKGROUND: Among patients diagnosed with advanced non-small-cell lung carcinoma (NSCLC), African-Americans have lower survival rates than non-African-Americans. Whether this difference is due to innate characteristics of the disease in the two ethnicities or to disparities in health care is not known. We investigated whether the disparity in survival would persist when patients were treated with similar systemic therapies (i.e., in phase II and phase III Cancer and Leukemia Group B [CALGB] trials). METHODS: We assessed 504 consecutive patients (458 non-African-American and 46 African-American) receiving systemic chemotherapy in CALGB studies for advanced NSCLC during the period from 1989 through 1998. Clinical and demographic characteristics, treatment received, and survival data were obtained from the CALGB database. Cox's proportional hazards model was used to assess the effect of race/ethnicity on survival after adjustment for other known prognostic factors. All statistical tests were two-sided. RESULTS: The unadjusted 1-year survival rate was 22% (95% confidence interval [CI] = 13% to 38%) for African-American patients and 30% (95% CI = 26% to 35%) for non-African-American patients, a statistically significant difference (8%; 95% CI on the difference = 5% to 12%; P =.03). Multivariable adjustment for the effect of treatment arm, histology, and metastatic site at presentation did not alter the worse outcome for African-American patients. However, the effect of race/ethnicity disappeared after adjustment for performance status and weight loss. African-American patients were more likely than non-African-Americans to present with a poor performance status (83% versus 60%) and substantial weight loss (41% versus 27%) and to be unmarried (59% versus 28%), disabled (31% versus 15%), unemployed (17% versus 7%), and Medicaid recipients (30% versus 8%). CONCLUSIONS: The relationship that we observed between poor performance, weight loss, and socioeconomic status suggests that social circumstances lead to African-Americans presenting with poorer prognostic features.

Adult↗

High-dose versus standard chemotherapy in metastatic breast cancer: comparison of Cancer and Leukemia Group B trials with data from the Autologous Blood and Marrow Transplant Registry.

PURPOSE: To assess survival of patients with metastatic breast cancer treated with high-dose chemotherapy (HDC) versus standard-dose chemotherapy (SDC). PATIENTS AND METHODS: SDC in four Cancer and Leukemia Group B (CALGB) trials was compared with hematopoietic stem-cell support in patients from the Autologous Blood and Marrow Transplant Registry. Cox proportional hazard regression incorporated potentially confounding effects. A total of 1,509 women were enrolled onto CALGB trials, and 1,188 women received HDC. No significant survival differences existed by CALGB trial or HDC regimen. Consideration was restricted to candidates for both SDC and HDC. The resulting sample included 635 SDC and 441 HDC patients. The outcome of interest was overall survival. RESULTS: The HDC group displayed better performance status. The SDC group had slightly better survival in first year after treatment. The HDC group had lower hazard of death from years 1 to 4 and had somewhat higher probability of 5-year survival (adjusted probabilities [95% confidence intervals], 23% [17% to 29%] v 15% [11% to 19%], P =.03). CONCLUSION: After controlling for known prognostic factors in this nonrandomized analysis of two large independent data sets, women receiving HDC versus SDC for metastatic breast cancer have a similar short-term probability of survival, and might have a modestly higher long-term probability of survival.

Adult↗

Prediction of the final MSLT result from the results of the first three naps.

OBJECTIVES: To determine if the mean sleep latency (mSL) and the presence of significant sleep onset rapid eye movement periods (SOREMPs) can be predicted from the results of the first three naps in selected patients undergoing multiple sleep latency test (MSLT). METHODS: Retrospective analysis of a number of MSLTs to identify the tests in which the mSL category and the presence of > or =2 naps with SOREMPS can be accurately predicted from the sleep latencies (SLs) of and SOREMPs in the first three naps. RESULTS: The study included 588 consecutive MSLTs performed on 552 patients during a 3-year period. (1) The mSL was normal (> or =10 min) for all MSLTs (n=90, 15%) if either (a) the SL was normal in each of the first three naps, or (b) SL was 20 min for any two of the first three naps. (2) The mSL was low (<5 min) or borderline (> or =5 and <10 min) for 99% MSLTs with SL in the low or borderline categories, respectively. (3) The accuracy of predicting > or =2 naps with SOREMPs was 100% (normal SL), 96% (borderline SL), and 89% (low SL). (4) The mSL category (normal or low) and the presence of > or =2 naps with SOREMPs were predicted with 100% accuracy in 23% of all MSLTs. CONCLUSIONS: The category of mSL can be predicted with >99% accuracy, if SL is normal, borderline, or low in each of the first three naps, or if the patient does not sleep in any two of the first three naps. MSLT can probably be shortened to three naps in up to 23% to reduce time, labor, discomfort, and cost of the test.

Journal Article↗

Hepatotoxicity of chemotherapy.

The selection of a chemotherapeutic regimen for the oncology patient is based on a thorough assessment of potential hazards relating to the patient's clinical condition and the toxicities of chemotherapy. Liver function abnormalities are commonly seen in this patient population and deducing their aetiology may be difficult. Immunosuppression, paraneoplastic phenomena, infectious disease, metastases and polypharmacy may all confound the clinical picture. While criteria for standardising liver injury have been established, dose modifications often rely on empirical clinical judgement. Therefore, a comprehensive understanding of hepatotoxic manifestations for the most common chemotherapeutic agents is essential. This article reviews the hepatotoxicity of commonly utilised antineoplastic agents.

Antineoplastic Agents↗

Lung cancer.

Lung cancer is the leading cause of cancer-related mortality. Since tobacco smoking is the cause in vast majority of cases, the incidence of lung cancer is expected to rise in those countries with high or rising incidence of tobacco smoking. Even though populations at risk of developing lung cancer are easily identified, mass screening for lung cancer is not supported by currently available evidence. In the case of non-small cell lung cancer, a cure may be possible with surgical resection followed by post-operative chemotherapy in those diagnosed at an early stage. A small minority of patients who present with locally advanced disease may also benefit from pre-operative chemotherapy and/or radiation therapy to down stage the tumor to render it potentially operable. In a vast majority of patients, however, lung cancer presents at an advanced stage and a cure is not possible with currently available therapeutic strategies. Similarly, small cell lung cancer confined to one hemi-thorax may be curable with a combination of chemotherapy and thoracic irradiation followed by prophylactic cranial irradiation, if complete remission is achieved at the primary site. Small cell lung cancer that is spread beyond the confines of one hemi-thorax is, however, considered incurable. In this era of molecular targeted therapies, new agents are constantly undergoing pre-clinical and clinical testing with the aim of targeting the molecular pathways thought be involved in etiology and pathogenesis of lung cancer.

Biological Therapy↗

Classical chemotherapy: mechanisms, toxicities and the therapeutic window.

Chemotherapy can be best used by understanding the principles of pharmacology, tumor biology, cellular kinetics and drug resistance. Here we try to focus on the major classes of chemotherapeutic drugs, their mechanisms of action, toxicities; and the therapeutic window.

Antineoplastic Agents↗