Between April 1981 and May 1984, 61 patients with advanced diffuse large-cell lymphoma completed treatment with MACOP-B (methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide,...

MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma.

PURPOSEThe trial was undertaken to determine (1) the relative efficacy/toxicity of two commonly used combination chemotherapy regimens in patients with extensive small-cell lung cancer (SCLC) and (2) whether the rapid alternation of these two regimens could provide superior therapeutic results compared with either regimen alone.PATIENTS AND METHODSIn this phase III trial, 437 eligible patients were stratified by performance status (PS) and sex and were randomly assigned to receive either 12 weeks of cisplatin and etoposide (EP); 18 weeks of cyclophosphamide, doxorubicin, and vincristine (CAV); or 18 weeks of alternation of these two regimens (CAV/EP).RESULTSThere were no significant differences in treatment outcome for EP, CAV, or CAV/EP in terms of response rate (61%, 51%, 59%, respectively), complete response rate (10%, 7%, 7%, respectively), or median survival (8.6 months, 8.3 months, 8.1 months, respectively), with a non-statistically significant trend toward a longer median time to progression with a...

Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group

This book provides a theoretical background of branching processes and discusses their biological applications. Branching processes are a well-developed and powerful set of tools in the field of applied probability. The range of applications considered includes molecular biology, cellular biology, human evolution and medicine. The branching processes discussed include Galton-Watson, Markov, Bellman-Harris, Multitype, and General Processes. As an aid to understanding specific examples, two introductory chapters, and two glossaries are included that provide background material in mathematics and in biology. The book will be of interest to scientists who work in quantitative modeling of biological systems, particularly probabilists, mathematical biologists, biostatisticians, cell biologists, molecular biologists, and bioinformaticians. The authors are a mathematician and cell biologist who have collaborated for more than a decade in the field of branching processes in biology for this new edition.This second expanded edition adds new material published during the last decade, with nearly 200 new references. More material has been added on infinitely-dimensional multitype processes, including the infinitely-dimensional linear-fractional case. Hypergeometric function treatment of the special case of the Griffiths-Pakes infinite allele branching process has also been added. There are additional applications of recent molecular processes and connections with systems biology are explored, and a new chapter on genealogies of branching processes and their applications.Reviews of First Edition:"This is a significant book on applications of branching processes in biology, and it is highly recommended for those readers who are interested in the application and development of stochastic models, particularly those with interests in cellular and molecular biology." (Siam Review, Vol. 45 (2), 2003)This book will be very interesting and useful for mathematicians, statisticians and biologists as well, and especially for researchers developing mathematical methods in biology, medicine and other natural sciences. (Short Book Reviews of the ISI, Vol. 23 (2), 2003)

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Branching processes in biology

PURPOSE: To investigate whether chemotherapy with etoposide and cisplatin (EP) is superior to cyclophosphamide, epirubicin, and vincristine (CEV) in small-cell lung cancer (SCLC). PATIENTS AND METHODS: A total of 436 eligible patients were randomized to chemotherapy with EP (n = 218) or CEV (n = 218). Patients were stratified according to extent of disease (limited disease [LD], n = 214; extensive disease [ED], n = 222). The EP group received five courses of etoposide 100 mg/m2 intravenously (IV) and cisplatin 75 mg/m2 IV on day 1, followed by oral etoposide 200 mg/m2 daily on days 2 to 4. The CEV group received five courses of epirubicin 50 mg/m2, cyclophosphamide 1,000 mg/m2, and vincristine 2 mg, all IV on day 1. In addition, LD patients received thoracic radiotherapy concurrent with chemotherapy cycle 3, and those achieving complete remission during the treatment period received prophylactic cranial irradiation. RESULTS: The treatment groups were well balanced with regard to age, sex, and prognostic f...

Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up.

Traditionally, intertumour heterogeneity in breast cancer has been documented in terms of different histological subtypes, treatment sensitivity profiles, and clinical outcomes among different patients. Results of high-throughput molecular profiling studies have subsequently revealed the true extent of this heterogeneity. Further complicating this scenario, the heterogeneous expression of the oestrogen receptor (ER), progesterone receptor (PR), and HER2 has been reported in different areas of the same tumour. Furthermore, discordance, in terms of ER, PR and HER2 expression, has also been reported between primary tumours and their matched metastatic lesions. High-throughput molecular profiling studies have confirmed that spatial and temporal intratumour heterogeneity of breast cancers exist at a level beyond common expectations. We describe the different levels of tumour heterogeneity, and discuss the strategies that can be adopted by clinicians to tackle treatment response and resistance issues associated with such heterogeneity, including a rationally selected combination of agents that target driver mutations, the targeting of deleterious passenger mutations, identifying and eradicating the 'lethal' clone, targeting the tumour microenvironment, or using adaptive treatments and immunotherapy. The identification of the most-appropriate strategies and their implementation in the clinic will prove highly challenging and necessitate the adoption of radically new practices for the optimal clinical management of breast malignancies.

Clinical management of breast cancer heterogeneity

Rationale for the use of alternating non-cross-resistant chemotherapy.

Using a computerized mathematical model the authors found that either a small [5%] or large [50%] hormone-dependent reduction in tumour cell population at the beginning of adjuvant chemotherapy for breast cancer greatly increases the probability fo achieving a cure. The fact that even a minor response to hormonal therapy early in the treatment of the tumor is effective underlines the importance of using estrogen receptors to to select potential responders in whom a cure is at least a strong theoretical possibility.

Gudauskas Ga

Papers

Rationale for the use of alternating non-cross-resistant chemotherapy.

Steroid receptors in adjuvant hormonal therapy for breast cancer.