Seminars in radiation oncology
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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.
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Clinical Trial
Preoperative paclitaxel, carboplatin, and radiation therapy in advanced head and neck cancer (stage III and IV).
Preoperative chemotherapy and chemoradiation protocols are generally associated with high clinical response rates but limited pathologic responses for large primary tumors. We have initiated a prospective phase II study of weekly paclitaxel and carboplatin plus concurrent, fractionated external-beam radiation, followed by organ-preserving or function-restorative surgery (when applicable to maximize locoregional tumor control). Operable patients staged by triple endoscopy received a percutaneous gastrostomy and vigorous dental and nutritional support during therapy. ⋯ All were resected with function-preserving reconstruction (two patients required total laryngectomy and one patient refused surgery). At a median follow-up of more than 16 months, progression-free and overall survival rates were 64% and 68%, respectively. Preoperative paclitaxel, carboplatin, and radiation was associated with a high clinical response rate at the primary site and a high level of organ preservation or functional restoration, if ablation was performed.
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Randomized Controlled Trial Clinical Trial
Concurrent chemoradiation using paclitaxel and carboplatin in locally advanced non-small cell lung cancer.
Evidence suggests that locally advanced non-small cell lung cancer may be more effectively treated with induction chemotherapy followed by radiation or concurrent chemoradiation compared with radiation alone. The majority of combined modality regimens evaluated in mature clinical trials incorporated cisplatin-based combinations, but none has incorporated newer active systemic agents or fully examined the potential role of induction chemotherapy followed by concurrent chemoradiation. The Fox Chase Cancer Center and its affiliate network have evaluated induction chemotherapy with paclitaxel plus carboplatin with or without granulocyte colony-stimulating factor priming followed by concurrent systemic chemotherapy and radiation therapy in patients with locally advanced non-small cell lung cancer. ⋯ Other studies evaluating different chemoradiation regimens have reported varying results. Paclitaxel/carboplatin-based combinations, administered cyclically at or near full systemic dose in combination with radiation, are feasible. Randomized studies are needed to determine the proper sequencing, potential survival benefits, and relative safety profiles of these combined modality regimens.