Radiotherapy and concomitant intra-arterial docetaxel combined with systemic 5-fluorouracil and cisplatin for oropharyngeal cancer: a preliminary report--improvement of locoregional control of oropharyngeal cancer.
ABSTRACT To confirm the advantage of chemoradiotherapy using intra-arterial docetaxel with intravenous cisplatin and 5-fluorouracil.
A total of 26 oropharyngeal cancer patients (1, 2, 2, and 21 patients had Stage I, II, III, and IVa-IVc, respectively) were treated with two sessions of this chemoradiotherapy regimen. External beam radiotherapy was delivered using large portals that included the primary site and the regional lymph nodes initially (range, 40-41.4 Gy) and the metastatic lymph nodes later (60 or 72 Gy). All tumor-supplying branches of the carotid arteries were cannulated, and 40 mg/m(2) docetaxel was individually infused on Day 1. The other systemic chemotherapy agents included 60 mg/m(2) cisplatin on Day 2 and 500 mg/m(2) 5-fluorouracil on Days 2-6.
The primary response of the tumor was complete in 21 (81%), partial in 4 (15%), and progressive in 1 patient. Grade 4 mucositis, leukopenia, and dermatitis was observed in 3, 2, and 1 patients, respectively. During a median follow-up of 10 months, the disease recurred at the primary site and at a distant organ in 2 (8%) and 3 (12%) patients, respectively. Three patients died because of cancer progression. Two patients (8%) with a partial response were compromised by lethal bleeding from the tumor bed or chemotherapeutic toxicity. The 3-year locoregional control rate and the 3-year overall survival rate was 73% and 77%, respectively.
This method resulted in an excellent primary tumor response rate (96%) and moderate acute toxicity. Additional follow-up is required to ascertain the usefulness of this modality.
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ABSTRACT: We designed a randomized clinical trial to test whether the addition of three cycles of chemotherapy during standard radiation therapy would improve disease-free survival in patients with stages III and IV (i.e., advanced oropharynx carcinoma). A total of 226 patients have been entered in a phase III multicenter, randomized trial comparing radiotherapy alone (arm A) with radiotherapy with concomitant chemotherapy (arm B). Radiotherapy was identical in the two arms, delivering, with conventional fractionation, 70 Gy in 35 fractions. In arm B, patients received during the period of radiotherapy three cycles of a 4-day regimen containing carboplatin (70 mg/m(2) per day) and 5-fluorouracil (600 mg/m(2) per day) by continuous infusion. The two arms were equally balanced with regard to age, sex, stage, performance status, histology, and primary tumor site. Radiotherapy compliance was similar in the two arms with respect to total dose, treatment duration, and treatment interruption. The rate of grades 3 and 4 mucositis was statistically significantly higher in arm B (71%; 95% confidence interval [CI] = 54%-85%) than in arm A (39%; 95% CI = 29%-56%). Skin toxicity was not different between the two arms. Hematologic toxicity was higher in arm B as measured by neutrophil count and hemoglobin level. Three-year overall actuarial survival and disease-free survival rates were, respectively, 51% (95% CI = 39%-68%) versus 31% (95% CI = 18%-49%) and 42% (95% CI = 30%-57%) versus 20% (95% CI = 10%-33%) for patients treated with combined modality versus radiation therapy alone (P =.02 and.04, respectively). The locoregional control rate was improved in arm B (66%; 95% CI = 51%-78%) versus arm A (42%; 95% CI = 31%-56%). The statistically significant improvement in overall survival that was obtained supports the use of concomitant chemotherapy as an adjunct to radiotherapy in the management of carcinoma of the oropharynx.JNCI Journal of the National Cancer Institute 01/2000; 91(24):2081-6. · 14.34 Impact Factor
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ABSTRACT: To determine the relative risk of prognostic factors for local disease control following RADPLAT. Prospective study, academic medical center. Analyses of nine categories of risk factors among 240 patients with Stage II-IV carcinoma consecutively treated with RADPLAT (cisplatin 150 mg/m IA and sodium thiosulfate 9 g/m IV, weekly x4; radiotherapy 2 Gy/fraction/d, 5x weekly, 68-74 Gy over 6 to 7 weeks). Median follow-up: 58 months (range, 12-96 mo). The percentage of patients who had local disease control was 87.5%. Univariant analysis showed T classification (P =.01), laterality of neck disease (P =.026), number of neck levels involved (P =.008), total dose of radiation greater versus less than 60 Gy (P =.027), and presence of pathologically positive lymph nodes following chemoradiation (P =.01) to be significant. Logistic regression analysis showed total dose of radiation (P =.03) and the presence of pathologically positive lymph nodes following chemoradiation (P =.05) to be significant. For Kaplan-Meier estimates of local disease control at 5 years, T classification (P =.038), number of levels with nodal disease (P =.006), and total dose of radiation therapy (P =.0001) were significant. The log-rank test identified as significant the total dose of radiation therapy (P <.0001), the presence of pathologically positive lymph nodes following chemoradiation (P =.005), and the number of neck levels with positive nodes (P =.006). The Cox regression model showed significance for the total dose of radiation (P =.001), the presence of pathologically positive lymph nodes following chemoradiation (P =.007), and the T classification (P =.029). Risk factors significantly associated with local disease control after RADPLAT appears to differ from more traditional therapy and is suggestive of a paradigm shift.The Laryngoscope 03/2004; 114(3):411-7. · 1.98 Impact Factor
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ABSTRACT: Since the publication of the Veterans Affairs study in the early 1990s, much has been learned regarding the role of chemotherapy, radiation therapy, and more importantly, the role of combined-modality treatment with chemoradiation in the therapy of locally advanced head and neck cancer. There continues to be widespread variation and controversy in the timing, schedule, and intensity of chemotherapy and chemoradiation. Herein, we present the various approaches currently used in the year 2003 with a specific emphasis on the role of sequential combined-modality therapy combining chemotherapy, chemoradiotherapy, and surgery in the treatment of these malignancies.The Oncologist 02/2003; 8(1):35-44. · 4.10 Impact Factor