Clinical trials in a radiotherapy center

The radiotherapy center should be peculiarly adapted to the conduct of clinical trials because of its organization and mode of operation. Centralization of therapeutic radiology, which is highly desirable, should ensure the attendance of large numbers of patients, which is essential for the conduct of any trial. A plea for simplicity of protocols is made and difficulties in the implementation of programs involving interdisciplinary management is emphasized. Although, with the application of considerable effort, clinical trials may provide answers to some clinical problems, it is probable that many advances in the field of radiotherapy, as in the past, will be derived from careful clinical observation and recording, and from frequent assessment of current treatment methods.     

Independent clinical trials: a commentary

The so-called norms of good clinical practice have been incorporated into the Italian regulatory legislation governing clinical trials sponsored by pharmaceutical companies, but there are no legislative provisions governing independent clinical trials: ie those not sponsored by the industry. The pharmaceutical industry has recently increased considerably its commitment to sponsored trials by establishing a series of economic relationships with individual researchers and hospital or university institutions. It has also set up and strengthened a series of bodies and service companies with the aim of making the clinical trials "machine" more efficient. Such developments have aroused alarm in the medical literature because of the risk that they may have negative effects on the freedom of research and research results. At the same time, there is also the risk that independent clinical trials will be greatly penalized by having to compete with sponsored trials in terms of patient enrollment, and because they are currently having to face a series of difficulties connected with the lack or scarcity of economic resources provided by the State or non-profit organizations, with problems relating to patient insurance and to the availability of the necessary drugs. However, the objective of independent trials is to improve the medical art by answering specific diagnostic and therapeutic questions, whereas that of industry-sponsored trials is to generate money, directly or indirectly, by means of the registration of new drugs. It is therefore now necessary to ensure better surveillance of the influence of pharmaceutical companies over the trials they sponsor (as a minimum by ensuring the transparency of a series of potential conflicts of interest between them and clinical researchers) and, simultaneously, protect independent trials from coming to an inglorious end by means of specific support initiatives such as those proposed in this article.     

Vindesine a review of phase-II trials

Summary Vindesine is a new vinca alkaloid with broadspectrum antineoplastic activity in experimental tumor models. Phase-I studies have shown that a weekly dosage regimen of 3–4 mg/m² IV produces manageable toxicity, with leukopenia and peripheral neuropathy being dose-limiting. Two hundred seventy-five patients have been enlisted in Phase-II trials at the Memorial Sloan-Kettering Cancer Center. Major objective responses (complete and partial remissions) were seen in bronchogenic carcinomas, melanoma, testicular carcinoma, esophageal carcinoma, acute lymphocytic leukemia, malignant lymphoma (Hodgkin's and non-Hodgkin's) and Wilms' tumor. Patients with hematologic and germ cell neoplasms were treated on a daily administration schedule (1.0–1.3 mg/m² IV for 5–7 days). Vindesine was well tolerated, with less than 5% of patients having a WBC nadir of<1000 cells/mm³ and with a platelet-sparing effect noted. Dose-related peripheral neuropathy occurred frequently and was generally mild to moderate in degree. Vindesine appears to be an active agent whose role will be further defined by completion of ongoing trials.Presented in part at the Vindesine International Workshop, July 7, 1978, Frankfurt     

International clinical trials for a medical oncologist in Japan

It is very important to participate into international clinical trials for cancer treatment not only for contribution to worldwide development of new anticancer agents but also for escape from social isolation out of new drug development. Here, we discussed about international clinical trials in Japan as an aspect of medical oncologist in medical school. And also, according to only one our experience of international clinical trial, IDEAL 1, which was a randomized phase II study of gefitinib for patients with previously treated metastatic non-small cell lung cancer, I tried to consider about current challenges of study investigators for cancer treatment, study conducting institution, pharmaceutical company, and regulatory agent in Japan.     

Methodology of antiemetic trials: a review

Chemotherapy-related nausea and vomiting can be controlled with available antiemetics in a high percentage of patients, while emesis remains a critical problem in some subgroups and with certain drugs. In the ceaseless attempt to find newer drugs and better treatment modalities, a sound methodology in antiemetic research is essential. Several factors should always be considered when planning an antiemetic trial: first, the different emetic power of various chemotherapy agents, their dosages and route and schedule of administration and second, the type of antiemetic used, its dosage and timing, and its possible combination with other antiemetics. Important factors which influence outcome but which are often under-evaluated are those related to patient population such as age, gender, and previous experience with chemotherapy. Considering the relevance of subjective phenomena in nausea and vomiting, it is essential that any study be randomized and double blinded. The parallel type of study design is preferable to the cross-over and a large number of patients is usually required to achieve meaningful results. Efficacy and toxicity should be properly evaluated by trained personnel in a standardized way, using a validated, relatively simple methodology.     

Quality of life in oncology trials: a clinical guide

Over the last 2 decades, there has been an explosion of quality of life (QOL) studies in the oncology literature. The purpose of this review is to provide a basic guide regarding the state-of-the-art of QOL in oncology trials from a clinical perspective. This article aims to provide fundamental definitions, describe useful existing tools, and highlight the challenges in interpreting QOL studies. What exactly is QOL, and why is it important to measure in cancer trials? Key methodological issues will be addressed, including choosing the optimal instrument, basic psychometric properties, timing of QOL assessments, and statistical considerations, such as minimizing missing data. The critical issue of interpreting the clinical significance of QOL results will be explored, using both anchor- and distribution-based strategies. The Radiation Therapy Oncology Group (RTOG) model involving a triad of outcomes (clinical, humanistic/QOL, and economic) will also be described. The future challenge will be to translate QOL results into clinically meaningful interventions.     

Statistics in clinical trials

Statistical developments over the past several years are described in this review. Efforts in phase I studies have focused on efficient estimation of maximum tolerated dose. Issues investigated for phase II trials include incorporation of multiple endpoints and randomization. For phase III trials, methods to reduce time or use the sample size more efficiently have been investigated. However, design innovations come with costs, including possible increased risk of incorrect conclusions. Other recent challenging statistical developments in clinical trials relate to use of complementary outcomes such as quality of life and to associated biologic questions, including the emergence of the field of genomics.     

Endpoints in adjuvant treatment trials: a systematic review of the literature in colon cancer and proposed definitions for future trials

Disease-free survival is increasingly being used as the primary endpoint of most trials testing adjuvant treatments in cancer. Other frequently used endpoints include overall survival, recurrence-free survival, and time to recurrence. These endpoints are often defined differently in different trials in the same type of cancer, leading to a lack of comparability among trials. In this Commentary, we used adjuvant studies in colon cancer as a model to address this issue. In a systematic review of the literature, we identified 52 studies of adjuvant treatment in colon cancer published in 1997-2006 that used eight other endpoints in addition to overall survival. Both the definition of these endpoints and the starting point for measuring time to the events that constituted these endpoints varied widely. A panel of experts on clinical research on colorectal cancer then reached consensus on the definition of each endpoint. Disease-free survival--defined as the time from randomization to any event, irrespective of cause--was considered to be the most informative endpoint for assessing the effect of treatment and therefore the most relevant to clinical practice. The proposed guidelines may add to the quality and cross-comparability of future studies of adjuvant treatments for cancer.     

Statistics in clinical trials

Statistical developments over the past several years are described in this review. Efforts in phase I studies have focused on efficient estimation of maximum tolerated dose. Issues investigated for phase II trials include incorporation of multiple endpoints and randomization. For phase III trials, methods to reduce time or use the sample size more efficiently have been investigated. However, design innovations come with costs, including possible increased risk of incorrect conclusions. Other recent challenging statistical developments in clinical trials relate to use of complementary outcomes such as quality of life and to associated biologic questions, including the emergence of the field of genomics.