A Phase II Study of Concurrent Chemoradiation with Weekly Docetaxel, Carboplatin, and Radiation Therapy Followed by Consolidation Chemotherapy with Docetaxel and Carboplatin for Locally Advanced Inoperable Non-small Cell Lung Cancer (NSCLC)
The current standard of care for good performance status patients with locally advanced non-small cell lung carcinoma is concurrent chemoradiation, although a clearly superior regimen has not been identified. Docetaxel has been shown to possess good single-agent activity against non-small cell lung cancer (NSCLC) and radiosensitizing properties, both alone and synergistically with carboplatin. We undertook this phase II study to determine the safety and efficacy of weekly docetaxel-carboplatin and concurrent radiation therapy followed by docetaxel-carboplatin consolidation for the treatment of locally advanced NSCLC.
Sixty-seven patients having previously untreated stage IIIA or IIIB unresectable NSCLC were enrolled, with 61 patients evaluated for endpoints. Docetaxel 20 mg/m IV infusion over 30 minutes followed by carboplatin area under the curve = 2 over 30 minutes was administered weekly during concurrent thoracic radiotherapy. After 3 week rest, consolidation docetaxel 75 mg/m(2) IV infusion over 60 minutes and carboplatin area under the curve = 6 over 30 minutes was administered every 3 weeks for two cycles. Concurrent thoracic radiation consisted of 45 Gy (1.8 Gy fractions 5 d/wk for first 5 weeks) followed by 18 Gy boost (2.0 Gy fractions 5 d/wk for 2 weeks) for a total dose of 63 Gy.
One and 2 years overall survival rates were 45 and 20%, respectively. Progression free survival at 1 year was 27%. Median survival time was 12 months. Median time to progression was 8 months. The primary hematologic toxicity was leukopenia. The primary nonhematologic toxicity was esophagitis.
The administered regimen of weekly docetaxel-carboplatin and concurrent radiation therapy followed by docetaxel-carboplatin consolidation has acceptable toxicity profile. However, the overall survivals at 1 and 2 years are somewhat disappointing.
"It has been demonstrated that this intensive multimodal treatment regimen results in significantly longer disease free and overall survival [1, 9, 10, 18]. However, concurrent administration of CT-RT is associated with a higher incidence of severe esophagitis [11, 17]. Therefore, according to current treatment guidelines, only patients with minimal comorbidity and with a good performance status are considered eligible for concurrent CT-RT . "
[Show abstract][Hide abstract] ABSTRACT: Radiation-esophagitis and weight loss are frequently observed toxicities in patients treated with concurrent chemo-radiotherapy (CT-RT) for non-small cell lung cancer (NSCLC) and might be related. The purpose was to investigate whether weight loss already starts early after initiation of CT-RT and precedes radiation-esophagitis.
In a retrospective cohort, weight and esophagitis grade ≥2 were assessed during the first weeks of (CT-)RT in patients treated with concurrent (n = 102) or sequential (n = 92) therapy. In a prospective validation study, data on body weight, esophagitis grade ≥2, nutritional intake and muscle strength were obtained before, during and following CT-RT.
In the retrospective cohort, early weight loss was observed in concurrently treated patients (p = 0.002), independent of esophagitis ≥ grade 2. Early weight loss was also observed in the prospective cohort (p = 0.003) and was not accompanied by decreases in nutritional intake. In addition lower limb muscle strength rapidly declined (p = 0.042). In the later weeks of treatment, further body weight loss occurred (p < 0.001) despite increased nutritional supplementation and body weight was only partly recovered after 4 weeks post CT-RT (p = 0.003).
Weight loss during concurrent CT-RT for NSCLC starts early and prior to onset of esophagitis, requiring timely and intense nutritional rehabilitation.
Journal of Cachexia, Sarcopenia and Muscle 01/2014; 5(2). DOI:10.1007/s13539-013-0127-5 · 7.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The majority of patients with nonsmall cell lung cancer (NSCLC) present with locally advanced mediastinal disease. Radiation therapy is the backbone, and nowadays a combination with chemotherapy is considered standard treatment. In this review we present a short history of the developments in this field with an update of all new developments. We address the questions how to optimally combine chemotherapy, targeted agents and radiation therapy.
The results from recently published papers dealing with combined chemoradiotherapy (CRT) and the data of two meta-analyses are reviewed. Some drugs are very suitable candidates for CRT such as cisplatin, pemetrexed and etoposide, whereas others should be avoided or used with caution (adriamycin, gemcitabine).
Our evaluation indicates that there are quite a number of positive developments in the treatment of locally advanced NSCLC but there is still much to improve. Variables such as patient condition, tumor biology, dose of radiation therapy, method of application (intensity modulated radiation therapy, four-dimensional planning) and dose of chemotherapy all influence treatment outcome and should be taken into account in designing the best treatment. Well-defined studies should be undertaken balancing the possible positive effect of therapy and toxicity.
Current opinion in oncology 03/2011; 23(2):140-9. DOI:10.1097/CCO.0b013e328341eed6 · 4.47 Impact Factor
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