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Paclitaxel With or Without Daily Subcutaneous Amifostine in the Treatment of Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Proceedings of the 47th Annual ASTRO Meeting
3. Richter E, Feyerabend T. Normal lymph node topography: CT Atlas. Berlin; New York: Springer, 2004. 4. Martinez-Monge R, Fernandes PS, Gupta N, Gahbauer R. Cross-sectional nodal atlas: a tool for the definition of clinical target volumes in three-dimensional radiation therapy planning. Radiology;211:815– 828;1999.
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Concomitant Chemoradiation Using Weekly Carboplatin/Paclitaxel With or Without Daily Subcutaneous Amifostine in the Treatment of Locally Advanced Squamous Cell Carcinoma of the Head and Neck
R. Haddad,1 M. Posner,1 L. Wirth,1 S. Sonis,2 L. Goguen,3 C. Norris,3 C. Sullivan,3 L. Weeks,1 R. Costello,1 R. Tishler4 1 Medical Oncology, Dana Farber Cancer Institute, Boston, MA, 2Department of Oral Medicine Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, 3Division of Otolaryngology, Head and Neck Surgery, Brigham and Women’s Hospital, Boston, MA, 4Radiation Oncology, Dana Farber cancer Institute, Boston, MA
Purpose/Objective: Concurrent chemoradiotherapy (CRT) improves survival in locally advanced squamous cell carcinoma of the head and neck (SCCHN) but is associated with a high incidence of toxicity. Concomitant boost XRT is widely used to treat these patients. Amifostine is an aminothiol prodrug that has been shown in clinical studies to protect mucosal tissue and salivary glands from radiotoxicity. Amifostine is approved for intravenous (IV) use, however, subcutaneous (SC) administration offers advantages in terms of improved tolerability and ease of administration. This phase II, open-label, multicenter, randomized study evaluated the efficacy of SC amifostine in reducing the toxicities associated with chemoradiotherapy (CRT) in patients with locally advanced SCCHN Materials/Methods: Patients aged ⱖ18 years with newly diagnosed locally advanced SCCHN were eligible for enrollment. Patients were randomized to receive CRT with (arm A) or without (arm B) Amifostine. Amifostine 500 mg was reconstituted with 2.9 mL of normal saline and administered SC in 2 equal doses 30 to 60 minutes before each morning dose of RT. Carboplatin AUC 1.5 IV and paclitaxel 45 mg/m2 IV were administered weekly during weeks 1, 2, 3, and 4. XRT was administered at 1.8 Gy daily 5 d/wk for 18 days and then twice daily (1.8 and 1.5 Gy) for 12 days. Study end points include the rate of local/regional control at 1 year, the incidence of grade 2/3 xerostomia at 3 and 6 months, grade 3/4 oral mucositis at the end of RT, and median duration of dependence on percutaneous endoscopic gastrostomy (PEG) tube feeding. Results: A total of 42 patients (37 men, 5 women) are enrolled, 22 in arm A (mean age 55 y) and 20 in arm B (mean age 56 y). The majority of patients (85%) had Stage 4 disease, most commonly affecting the oropharynx (75%). The 2 treatment arms were well matched with regard to primary site and disease stage. Mean RT dose was 70 Gy. Median follow up is twelve months. Four patients have progressed (two in each arm) and three of those have died. Thirty-eight patients are alive with no recurrence (90%). Eight (36%) patients in arm A completed all doses of amifostine as scheduled; two patients stopped Amifostine the first week because of high fever and rash and twelve patients had their Amifostine held for few days because of local skin reactions and/or pain at the site of injection. All patients had PEG inserted prior to therapy. Nineteen patients had their PEG removed so far (10 Arm B, 9 Arm A). Median time to PEG removal is 30 weeks in arm B and 16 weeks in Arm A. Post stimulatory saliva production was greater in arm A than arm B at week 12 (2.16 g vs 1.58 g), week 24 (1.57 g vs 0.99 g), and week 52 (1.58 g vs 1.06 g) following treatment. Conclusions: This aggressive CRT regimen is highly effective in patients with locally advanced SCCHN with an excellent local-regional control. Amifostine appears to improve salivary function as measured by salivary flow and time to PEG removal. Amifostine was generally well tolerated. These preliminary findings suggest that SC amifostine may be effective in reducing the toxicities associated with CRT in this patient population treated with aggressive chemoradiation. The study continues to enroll patients.
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Concurrent Chemoradiation Therapy with Low-Dose CDDP and UFT for Glottic Carcinomas: Evaluation Using The Sixth Edition of The UICC TNM Staging System
R. Murakami,1,2 R. Nishimura,1,2 Y. Baba,2,1 E. Yumoto,3 N. Oya,1 Y. Yamashita2 1
Radiation Oncology, Kumamoto University Hospital, Kumamoto, Japan, 2Diagnostic Radiology, Kumamoto University Hospital, Kumamoto, Japan, 3Otorhinolaryngology, Kumamoto University Hospital, Kumamoto, Japan
Purpose/Objective: To improve local control and laryngeal preservation in patients with glottic carcinoma classified as T2N0 by the 5th edition of the UICC, we performed concurrent chemoradiation therapy (CRT) with low-dose CDDP (cisplatin) and UFT (uracil and tegafur) as radiosensitizers. To stratify the treatment of glottic carcinomas, we evaluated whether CRT could improve the outcome of patients with different prognostic factors namely paraglottic space invasion and/or minor thyroid cartilage erosion based on the staging system introduced in the 6th edition of the UICC. Materials/Methods: Between 1999 and 2003, 51 patients with glottic carcinoma classified as T2N0 by the 5th edition of the UICC underwent pretreatment radiological examination and CRT (CRT group). They received a total dose of 64 Gy at 2-Gy fractions per day delivered to opposed lateral fields. They also received i.v. infusions of CDDP (4 mg/m2) and oral UFT (450 mg of tegafur/body/day) starting with the 1st day of irradiation and continuing for 4 weeks. The historical control consisted of 49 patients with T2N0 glottic carcinoma treated between 1989 and 1998 with definitive radiation therapy (RT) alone (RT group).
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3. Richter E, Feyerabend T. Normal lymph node topography: CT Atlas. Berlin; New York: Springer, 2004. 4. Martinez-Monge R, Fernandes PS, Gupta N, Gahbauer R. Cross-sectional nodal atlas: a tool for the definition of clinical target volumes in three-dimensional radiation therapy planning. Radiology;211:815– 828;1999.
2229
Concomitant Chemoradiation Using Weekly Carboplatin/Paclitaxel With or Without Daily Subcutaneous Amifostine in the Treatment of Locally Advanced Squamous Cell Carcinoma of the Head and Neck
R. Haddad,1 M. Posner,1 L. Wirth,1 S. Sonis,2 L. Goguen,3 C. Norris,3 C. Sullivan,3 L. Weeks,1 R. Costello,1 R. Tishler4 1 Medical Oncology, Dana Farber Cancer Institute, Boston, MA, 2Department of Oral Medicine Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, 3Division of Otolaryngology, Head and Neck Surgery, Brigham and Women’s Hospital, Boston, MA, 4Radiation Oncology, Dana Farber cancer Institute, Boston, MA
Purpose/Objective: Concurrent chemoradiotherapy (CRT) improves survival in locally advanced squamous cell carcinoma of the head and neck (SCCHN) but is associated with a high incidence of toxicity. Concomitant boost XRT is widely used to treat these patients. Amifostine is an aminothiol prodrug that has been shown in clinical studies to protect mucosal tissue and salivary glands from radiotoxicity. Amifostine is approved for intravenous (IV) use, however, subcutaneous (SC) administration offers advantages in terms of improved tolerability and ease of administration. This phase II, open-label, multicenter, randomized study evaluated the efficacy of SC amifostine in reducing the toxicities associated with chemoradiotherapy (CRT) in patients with locally advanced SCCHN Materials/Methods: Patients aged ⱖ18 years with newly diagnosed locally advanced SCCHN were eligible for enrollment. Patients were randomized to receive CRT with (arm A) or without (arm B) Amifostine. Amifostine 500 mg was reconstituted with 2.9 mL of normal saline and administered SC in 2 equal doses 30 to 60 minutes before each morning dose of RT. Carboplatin AUC 1.5 IV and paclitaxel 45 mg/m2 IV were administered weekly during weeks 1, 2, 3, and 4. XRT was administered at 1.8 Gy daily 5 d/wk for 18 days and then twice daily (1.8 and 1.5 Gy) for 12 days. Study end points include the rate of local/regional control at 1 year, the incidence of grade 2/3 xerostomia at 3 and 6 months, grade 3/4 oral mucositis at the end of RT, and median duration of dependence on percutaneous endoscopic gastrostomy (PEG) tube feeding. Results: A total of 42 patients (37 men, 5 women) are enrolled, 22 in arm A (mean age 55 y) and 20 in arm B (mean age 56 y). The majority of patients (85%) had Stage 4 disease, most commonly affecting the oropharynx (75%). The 2 treatment arms were well matched with regard to primary site and disease stage. Mean RT dose was 70 Gy. Median follow up is twelve months. Four patients have progressed (two in each arm) and three of those have died. Thirty-eight patients are alive with no recurrence (90%). Eight (36%) patients in arm A completed all doses of amifostine as scheduled; two patients stopped Amifostine the first week because of high fever and rash and twelve patients had their Amifostine held for few days because of local skin reactions and/or pain at the site of injection. All patients had PEG inserted prior to therapy. Nineteen patients had their PEG removed so far (10 Arm B, 9 Arm A). Median time to PEG removal is 30 weeks in arm B and 16 weeks in Arm A. Post stimulatory saliva production was greater in arm A than arm B at week 12 (2.16 g vs 1.58 g), week 24 (1.57 g vs 0.99 g), and week 52 (1.58 g vs 1.06 g) following treatment. Conclusions: This aggressive CRT regimen is highly effective in patients with locally advanced SCCHN with an excellent local-regional control. Amifostine appears to improve salivary function as measured by salivary flow and time to PEG removal. Amifostine was generally well tolerated. These preliminary findings suggest that SC amifostine may be effective in reducing the toxicities associated with CRT in this patient population treated with aggressive chemoradiation. The study continues to enroll patients.
2230
Concurrent Chemoradiation Therapy with Low-Dose CDDP and UFT for Glottic Carcinomas: Evaluation Using The Sixth Edition of The UICC TNM Staging System
R. Murakami,1,2 R. Nishimura,1,2 Y. Baba,2,1 E. Yumoto,3 N. Oya,1 Y. Yamashita2 1
Radiation Oncology, Kumamoto University Hospital, Kumamoto, Japan, 2Diagnostic Radiology, Kumamoto University Hospital, Kumamoto, Japan, 3Otorhinolaryngology, Kumamoto University Hospital, Kumamoto, Japan
Purpose/Objective: To improve local control and laryngeal preservation in patients with glottic carcinoma classified as T2N0 by the 5th edition of the UICC, we performed concurrent chemoradiation therapy (CRT) with low-dose CDDP (cisplatin) and UFT (uracil and tegafur) as radiosensitizers. To stratify the treatment of glottic carcinomas, we evaluated whether CRT could improve the outcome of patients with different prognostic factors namely paraglottic space invasion and/or minor thyroid cartilage erosion based on the staging system introduced in the 6th edition of the UICC. Materials/Methods: Between 1999 and 2003, 51 patients with glottic carcinoma classified as T2N0 by the 5th edition of the UICC underwent pretreatment radiological examination and CRT (CRT group). They received a total dose of 64 Gy at 2-Gy fractions per day delivered to opposed lateral fields. They also received i.v. infusions of CDDP (4 mg/m2) and oral UFT (450 mg of tegafur/body/day) starting with the 1st day of irradiation and continuing for 4 weeks. The historical control consisted of 49 patients with T2N0 glottic carcinoma treated between 1989 and 1998 with definitive radiation therapy (RT) alone (RT group).
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