Anti-cancer drugs
-
The palliative goal of the treatment of metastatic prostate cancer is to prolong survival and decrease cancer-related complications. Androgen ablation therapy is widely accepted as the initial treatment of choice; when the disease becomes resistant to castration-resistant prostate cancer (CRPC), docetaxel-based chemotherapy aids in prolonging overall survival and controlling disease-related symptoms. Until a few years ago, no drug had showed efficacy in docetaxel-resistant patients. ⋯ Abiraterone inhibits the enzymatic activity of steroid 17α-monooxygenase, a member of the cytochrome P450 family that catalyzes the 17α-hydroxylation of steroid intermediates involved in testosterone synthesis from the adrenal glands. This review focuses on abiraterone acetate, the first compound that, through the inhibition of adrenal gland production of testosterone, increases the overall survival in CRPC patients. The role of possible predictive biomarkers and future perspectives are also discussed.
-
This study was designed to determine the maximum tolerated dose and toxicity profile of belotecan in combination with oral etoposide in patients with platinum-resistant or heavily treated ovarian cancer, fallopian tubal cancer, and primary peritoneal cancer. Belotecan (0.5 mg/m/day) was administered daily (days 1-5) followed by etoposide (50, 75 mg/day) for up to 5 days (days 6-10) every 3 weeks. Dose-limiting toxicities (DLT) were defined as follows: grade 4 neutropenia less than 1 week; either neutropenic fever less than 24 h or sepsis; grade 4 thrombocytopenia; and grade of at least 3 nonhematologic toxicity except alopecia. ⋯ Thus, the maximum tolerated dose was reached (50 mg of oral etoposide) and the trial was terminated. The response was evaluable in nine patients and an objective response was observed in four patients (44%) including two complete responses. The combined regimen of belotecan followed by oral etoposide showed promising activity in platinum-resistant or heavily pretreated ovarian cancer patients at the dose level of 50 mg of oral etoposide.
-
The purpose of this article is to present some of the challenges the trial statistician meets when designing a clinical trial of the head and neck cancer. In recent years, the field of head and neck cancer has been facing some exciting evolutions, such as the arrival of newly targeted therapies and findings of disease causality and prognosis. These evolutions are accompanied by challenges in trial methodology that continue even today, and will most likely grow in importance in the future. This article focuses essentially on the design of phase III trials and discusses three major topics: should the trial be designed for a broad or a targeted population? Is there a concern for lack of equipoise and if so, how will it affect the trial results? What are the key elements that need to be taken into consideration when choosing, defining, and measuring the primary endpoint?
-
The primary aim of the high-dose 5-fluorouracil (5-FU) and leucovorin (LV; HDFL48) phase I study was to determine the maximum tolerated dose and dose-limiting toxicity of 5-FU and LV with modified tri-monthly 48-h continuous infusion of high-dose 5-FU/LV in patients with metastatic colorectal cancer. The study also determined the pharmacokinetic parameters of 5-FU, especially steady-state plasma and bone marrow (BM) concentrations. Eligibility included serum triglyceride of more than or equal to 70 mg/dl, adequate BM function, and the major typical trial criteria. ⋯ Median progression-free survival and overall survival were 4.1 months (range: 1.8-12.5) and 10.5 months (range: 2.7-32.1), respectively. The efficacy and low myelotoxicity of HDFL48 were attributed to the sustained adequate steady-state plasma concentration and an average 2.63-fold concentration gradient between plasma and BM compartments at steady state. The recommended 5-FU dose for use in future trials was 3500 mg/m²/48 h/week, with a fixed dose of LV at 300 mg/m²/48 h/week.
-
The current standard treatment for early stage (I-III) renal cell cancer (RCC) is surgery. While the prognosis of stage I tumors is excellent, stage II and particularly stage III have a high risk of relapse. The adjuvant treatment of patients with RCC remains an area of investigation, with patient selection being a key aspect. ⋯ In the metastatic RCC setting, recent advances in the molecular understanding of oncogenic pathways have led to the development of new therapeutic strategies with the use of targeted therapies in the adjuvant setting. Neoadjuvant treatment is another treatment modality currently being evaluated for patients with early disease and in patients with metastatic RCC with inoperable primary tumors. The questions that remain unanswered include activity of these agents in early stages of the disease, patient selection, optimal start time of the adjuvant treatment, and finally, the optimal length of treatment.