Seminars in oncology
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Seminars in oncology · Dec 2004
Review Multicenter Study Clinical TrialOpen label multicenter trial of subcutaneous amifostine (Ethyol) in the prevention of radiation induced esophagitis and pneumonitis in patients with measurable, unresectable non-small cell lung cancer.
While concurrent delivery of chemotherapy and radiotherapy (RT) has a synergistic effect on tumor control and improves the median and overall survival in patients with locally advanced non-small cell lung cancer, appreciable acute and late morbidity occur to the esophagus and the lung during treatment (ie, acute radiation esophagitis, pulmonary toxicity). Emerging evidence suggests that the volume of normal lung exposed to certain threshold doses of RT might predict for the incidence of pneumonitis. Clinical data also indicate that amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD), an organic thiophosphate, acts as a selective cytoprotective agent for normal tissues against the toxicities of chemotherapy and RT. ⋯ We are conducting an open-label trial that is accruing patients with locally advanced non-small cell lung cancer, who will receive concurrent chemoradiotherapy (cisplatin/etoposide or carboplatin/paclitaxel plus RT delivered using 3-dimensional conformal radiotherapy treatment planning) and amifostine 500 mg before RT. Incidence and severity of acute radiation esophagitis, acute radiation pneumonitis, chronic radiation pneumonitis, and changes in pulmonary function will be recorded, as will elements of the RT treatment planning (eg, dose volume histogram data for the lung and esophagus). Pre- and post-therapy pulmonary function is a primary endpoint, and others include general safety assessments of subcutaneous amifostine administration.
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Seminars in oncology · Dec 2004
ReviewRecent updates in the clinical use of platinum compounds for the treatment of lung, breast, and genitourinary tumors and myeloma.
Platinum compounds have shown activity in a broad spectrum of human tumors in vitro and in vivo. The clinical utility of platinum agents in gynecologic and gastrointestinal cancers (particularly oxaliplatin in colorectal cancer) has been well documented and platinum agents continue to be evaluated in a variety of other cancers. Given preclinical evidence of synergy among some platinum compounds and new anticancer agents, clinical trials exploring platinum-based combination therapies may yield improved treatment for a variety of malignancies. Recent clinical data on new chemotherapeutic strategies for the treatment of lung, breast, and genitourinary cancers and myeloma will be presented in this review.
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Seminars in oncology · Dec 2004
Comparative Study Clinical TrialThe evaluation of amifostine for mucosal protection in patients with advanced loco-regional squamous cell carcinomas of the head and neck (SCCHN) treated with concurrent weekly carboplatin, paclitaxel, and daily radiotherapy (RT).
Concurrent chemotherapy and radiation has improved the outcome for patients presenting with locally advanced squamous cell carcinomas of the head and neck (SCCHN). These improvements have come at a cost of increased treatment-related toxicities. We previously reported the results of a phase II trial examining the role of concurrent carboplatin, paclitaxel, and daily radiotherapy (RT) in SCCHN. ⋯ Clinical complete response at both the primary site of disease and neck was achieved in 75% of patients 2 months following completion of RT. Weekly carboplatin and paclitaxel administered concurrently with definitive RT and daily amifostine is well tolerated, with over 85% of patients completing therapy with acceptable toxicity. The addition of amifostine appears to decrease treatment-related toxicity without impacting efficacy.
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Seminars in oncology · Dec 2004
Comparative Study Clinical TrialToxicity and compliance of subcutaneous amifostine in patients undergoing postoperative intensity-modulated radiation therapy for head and neck cancer.
Standard conventional radiation therapy for advanced head and neck tumors typically involves administering high radiation dose to the major salivary glands bilaterally. In most cases, this causes a marked reduction in oral saliva output. Xerostomia is one of the most prevalent late side effects of radiation for head and neck malignancies, and patients cite it as the major cause of decreased quality of life. ⋯ We hypothesize that the addition of a radiation protector, such as amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD) may further improve salivary function over that obtained with IMRT alone. To test this hypothesis, we have initiated a pilot clinical trial to compare unstimulated and stimulated salivary flow rates 6 months and 1 year after IMRT + amifostine with historic controls treated with IMRT alone. Twenty-seven patients have been accrued onto this trial, and the toxicity and compliance data are reported herein.
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Seminars in oncology · Dec 2004
Clinical TrialSelective dose escalation of chemoradiotherapy for esophageal cancer: role of treatment intensification.
This ongoing phase II study is designed to assess the outcomes (survival and failure patterns) of therapy for localized esophageal cancer with conventional dose radiation (50.4 Gy) with concurrent continuous infusion 5-fluorouracil (5-FU) and weekly carboplatin/paclitaxel. Patients with less than complete response or partial response received dose escalation of radiation to 59.4 Gy with the same chemotherapy. This report details the results of the first 18 patients treated. ⋯ Grade 2/3 acute esophagitis was experienced by 89% and 39% of patients, respectively; 28% of patients developed esophageal strictures requiring dilatations. The combination of continuous-infusion 5-FU and weekly carboplatin/paclitaxel with selective radiation dose escalation yields promising results without surgery and adjuvant chemotherapy. The toxicities of therapy, while manageable, were significant.