Seminars in radiation oncology
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Recent efforts to improve survival outcome in patients with locally advanced non-small cell lung cancer have focused on the use of chemoradiotherapy regimens containing vinblastine/cisplatin or etoposide/cisplatin. However, the overall treatment outcome with these regimens remains poor, emphasizing the need for new therapeutic options. Based on the activity of paclitaxel in advanced non-small cell lung cancer, its additive cytotoxicity with cisplatin, and the radiation-sensitizing effect of both agents, a phase I/IIa study was designed to examine the feasibility of paclitaxel/cisplatin concurrently with conventional thoracic irradiation in patients with locally advanced tumors. ⋯ In a univariate analysis, no relationship was noted between paclitaxel dose level, degree of lymphocytopenia, changes in pulmonary function indices, and incidence of pulmonary toxicity. However, there was a significant dose-volume relationship (using conventional dose-volume histograms) with late pulmonary toxicity at radiation doses between 15 Gy and 30 Gy. Based on a literature review, paclitaxel-based chemotherapy regimens seem to be associated with a slightly higher risk of pulmonary toxicity; however, comparison of such toxicity between trials has many limitations that require that the conclusion reached be viewed with caution.
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Clinical Trial
Daily paclitaxel and thoracic radiation therapy for non-small cell lung cancer: preliminary results.
Platinum-based combination chemotherapy plus thoracic radiation prolongs survival for patients with stage III non-small cell lung cancer. Paclitaxel demonstrates significant clinical antitumor activity in this disease and potentiates the effects of ionizing radiation by arresting cells at the sensitive G2/M cell cycle phase. The optimal schedule of paclitaxel administered concomitantly with thoracic radiation has not been established. ⋯ A daily paclitaxel dose of 10 mg or 6 mg/m2 and 68 Gy of thoracic radiotherapy are recommended for further study. Preliminary data from this dose-escalation trial suggest that this combined modality treatment with concurrent radiation and daily paclitaxel following primary induction therapy for stage II to III non-small cell lung cancer is feasible. The observed adverse effects within the radiation field suggest active radiosensitization by low-dose daily paclitaxel.
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Lung cancer must be viewed as a systemic disease, and control of latent metastases at both regional and systemic sites is the goal of therapy. Combined modalities have emerged as the dominant strategy with which to manage latent metastases, and paclitaxel has several properties, including a modest toxicity profile, significant activity, and radiosensitization potential, which contribute to its effectiveness in this setting. In phase I clinical trials, paclitaxel was administered weekly in combination with radiation therapy (60 Gy) in the outpatient setting to patients with stage III non-small cell lung cancer (NSCLC). ⋯ When paclitaxel is administered using this schedule, it appears to exhibit an altered pattern of toxicity, with much lower incidences of hematologic and neurologic toxicities, which may improve the overall therapeutic index of this combination. Until curative systemic therapy is developed, combined modality approaches offer the greatest potential for long-term control of advanced NSCLC. Based on the observed activity and toxicity profile, concurrent radiation therapy plus paclitaxel offers significant clinical utility for control of both local and distant metastatic disease.
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Clinical Trial
Paclitaxel and concurrent radiotherapy in locally advanced non-small cell lung cancer: the Canadian experience.
Several studies have been conducted to assess the safety and efficacy of paclitaxel plus radiation therapy in patients with non-small cell lung cancer (NSCLC) and to assess whether the radiosensitization demonstrated by paclitaxel in vivo can translate into clinical benefit. The National Cancer Institute of Canada Clinical Trials Group conducted a phase I/II trial in patients with inoperable stage IIIA or IIIB NSCLC to determine the maximum tolerated dose and efficacy of paclitaxel, given as a 3-hour infusion every 2 weeks during radical radiotherapy. The paclitaxel maximum tolerated dose using this schedule was 135 mg/m2; the recommended phase II dose was 120 mg/m2. ⋯ Grade 3 skin toxicity within the radiation field was reported in three patients receiving paclitaxel 120 mg/m2. This combination can be safely delivered to patients with NSCLC and has demonstrated activity in this setting. This combination has been used in Canada outside of clinical trials, and its use may be expanded as additional data from ongoing clinical trials further define the role of paclitaxel-based combined modality therapy in NSCLC.
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Multicenter Study Clinical Trial
Seven-week continuous-infusion paclitaxel concurrent with radiation therapy for locally advanced non-small cell lung and head and neck cancers.
The goal of these National Cancer Institute-sponsored phase I trials is to determine the feasibility, toxicity, and pharmacokinetics of continuous-infusion (24 hr/d, 7 d/wk, 7 weeks total) intravenous paclitaxel combined with standard, curative-intent thoracic radiation therapy (XRT) for previously untreated, locally advanced non-small cell lung cancer and squamous cell cancer of the head and neck (HNSCC). Eligible patients have locally advanced (T4NXM0 or TXN2-3M0) non-small cell lung cancer ineligible for potentially curative surgical resection or locally advanced HNSCC with an expected 5-year survival rate of less than 25%, as well as a good performance status, adequate hematologic, hepatic, and renal function, and no distant metastases. Non-small cell lung cancer patients receive a total tumor dose of 64.8 Gy megavoltage XRT in 7 weeks at 1.8 Gy once daily, 5 d/wk. ⋯ Clinical outcomes suggest significant activity for this combination. This therapy is feasible and has been well-tolerated through current dose levels. Dose escalation is ongoing.