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Safety and feasibility of subcutaneous amifostine administration prior to radiation therapy
Proceedings of the 44th Annual ASTRO Meeting
2131
Safety and Feasibility of Subcutaneous Amifostine Administration Prior to Radiation Therapy
M.A. Samuels1, T. Mesko2, M.E. Keisch1, K. Kopacka1 1 Department of Radiation Oncology, Mt. Sinai Medical Center, Miami Beach, FL, 2Division of Surgical Oncology, Mt. Sinai Medical Center, Miami Beach, FL Purpose/Objective: Amifostine has been shown in a phase III trial (Brizel, et al., JCO 1999) to be an effective radioprotectant in patients with head and neck cancer. Intravenous administration of amifostine has been associated with nausea, vomiting, and hypotension. In addition, IV administration can be a logistical challenge in a radiation oncology setting. Anne, et al. (ASTRO 2001) presented their results of a phase II subcutaneous amifostine trial for patients receiving radiation therapy for head and neck cancer which may offer advantages in terms of both toxicity and convenience in the radiation therapy setting. Materials/Methods: To date, we have treated 18 patients, 15 males/3 females, with subcutaneous amifostine prior to their daily radiation therapy. Ages ranged from 39-73 years, and the median Karnofsky status was 90%. Primary diagnoses included 14 head and neck cancers, 2 lymphomas of the head and neck region, 1 melanoma, and one hemangiopericytoma of the right eye. Ten of 18 patients received radiation therapy without chemotherapy and 8/18 patients received concurrent chemoradiotherapy. Patients were instructed to hydrate orally daily prior to radiation therapy. Prophylactic anti-emetics, such as ondansetron or prochlorperazine, were given daily prior to amifostine. A flat dose of amifostine 500 mg was reconstituted with 3 ml of normal saline and given in 2 1.5 ml subcutaneous injections. Injection sites included the deltoids and abdomen, and were rotated daily. Radiation treatment followed the amifostine injections by no less than 30 minutes. Results: Local injection site reactions, generally transient, occurred in 9/18 patients with the most common symptoms being redness, warmth, and discomfort. Two of 18 patients experienced a local rash. These were treated with warm compresses, diphenhydramine, and hydrocortisone cream. One of 18 patients developed a grade II general urticaria, and amifostine was discontinued. Four of 18 patients experienced treatment breaks due to hypotension, with one patient discontinued from treatment with amifostine. All cases of hypotension appeared to be related to the disease process (dehydration) rather than to amifostine treatment. Nausea was seen in 2/10 patients who did not receive chemotherapy and in 4/8 chemoradiotherapy patients. Two of 18 patients experienced low-grade fevers, for which non-amifostine causes were documented. Conclusions: Subcutaneous administration of amifostine is generally well-tolerated and convenient. It may be a preferable route of administration when used for radioprotection.
2132
Encouraging Early Results for Advanced Stage III-IV Nasopharyngeal Carcinoma using NeoadjuvantConcurrent Chemotherapy and Accelerated Radiotherapy
A. Lee, W.M. Sze, T.K. Yau, R. Yeung, K. Chan, C. Ng Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China Purpose/Objective: To study the possibility of improving tolerance and treatment outcome for advanced nasopharyngeal carcinoma by combining concurrent chemotherapy with accelerated radiotherapy and changing non-concurrent chemotherapy to neoadjuvant sequencing. Materials/Methods: During the period January 1998 to March 2001, 40 patients (10% Stage III and 90% Stage IV by AJCC 1997 System) with loco-regional infiltration too extensively for adequate coverage by the contemporary radiotherapy technique were treated with 3 cycles of chemotherapy using Cisplatin and 5-Fluorouracil prior to commencement of radiotherapy plus another 3 cycles of Cisplatin. All were irradiated with accelerated fractionation at 2 Gy per fraction, 6 daily fractions per week, to a total of 66-70 Gy. Results: Compliance with chemotherapy: 83% of patients completed 3 cycles of neoadjuvant and 55% completed ⬎⫽2 cycles of concurrent chemotherapy. Median total dose of Cisplatin given was 510 mg/m2 (range: 200 – 600). Grade ⬎⫽3 acute toxicities attributed to chemotherapy were observed in 23% of patients during the neoadjuvant phase and 30% during the concurrent phase. All patients completed the intended course of radiotherapy and the median overall radiotherapy time was 42 days (range: 38 –50). Grade ⬎⫽3 mucositis and skin reaction were observed in 58% and 16% of patients, respectively. The median weight loss during the whole course of treatment was 9% of initial body weight. With a median follow-up of 1.7 years (range: 0.5-3.4), the 2-year actuarial overall survival was 82% and progression-free survival 81%. The corresponding local, nodal and distant failure-free rates were 90%, 100%, and 89%, respectively. Altogether 9 (23%) patients developed Grade ⬎⫽3 late radiation complications, the 2-year actuarial rate at 33%. Four of them had impairment of hearing, but none had other neurological damage. Conclusions: Changing the chemotherapy sequence to neoadjuvant-concurrent could increase the total dose of Cisplatin given, particularly during the neoadjuvant phase. The treatment was well tolerated even when combined with accelerated fractionation. The early tumor control results achieved for this most advanced group are substantially better than historic data. The current approach is a promising strategy, and confirmation of therapeutic gain by prospective randomized trial is warranted.
2133
A Population-Based Three Dimensional Atlas of the Head and Neck Lymph Nodes for Conformal (IMRT) Radiotherapy
I. Poon3, N. Fischbein2, J. Ho4, N. Lee1, P. Akazawa1, P. Xia1, T. Phillips1 1 Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, 2Department of Diagnostic Radiology, University of California, San Francisco, San Francisco, CA, 3Department of Radiation Oncology, Hamilton Regional Cancer , Hamilton, ON, Canada, 4Royal St. George’s College, Toronto, ON, Canada
287
2131
Safety and Feasibility of Subcutaneous Amifostine Administration Prior to Radiation Therapy
M.A. Samuels1, T. Mesko2, M.E. Keisch1, K. Kopacka1 1 Department of Radiation Oncology, Mt. Sinai Medical Center, Miami Beach, FL, 2Division of Surgical Oncology, Mt. Sinai Medical Center, Miami Beach, FL Purpose/Objective: Amifostine has been shown in a phase III trial (Brizel, et al., JCO 1999) to be an effective radioprotectant in patients with head and neck cancer. Intravenous administration of amifostine has been associated with nausea, vomiting, and hypotension. In addition, IV administration can be a logistical challenge in a radiation oncology setting. Anne, et al. (ASTRO 2001) presented their results of a phase II subcutaneous amifostine trial for patients receiving radiation therapy for head and neck cancer which may offer advantages in terms of both toxicity and convenience in the radiation therapy setting. Materials/Methods: To date, we have treated 18 patients, 15 males/3 females, with subcutaneous amifostine prior to their daily radiation therapy. Ages ranged from 39-73 years, and the median Karnofsky status was 90%. Primary diagnoses included 14 head and neck cancers, 2 lymphomas of the head and neck region, 1 melanoma, and one hemangiopericytoma of the right eye. Ten of 18 patients received radiation therapy without chemotherapy and 8/18 patients received concurrent chemoradiotherapy. Patients were instructed to hydrate orally daily prior to radiation therapy. Prophylactic anti-emetics, such as ondansetron or prochlorperazine, were given daily prior to amifostine. A flat dose of amifostine 500 mg was reconstituted with 3 ml of normal saline and given in 2 1.5 ml subcutaneous injections. Injection sites included the deltoids and abdomen, and were rotated daily. Radiation treatment followed the amifostine injections by no less than 30 minutes. Results: Local injection site reactions, generally transient, occurred in 9/18 patients with the most common symptoms being redness, warmth, and discomfort. Two of 18 patients experienced a local rash. These were treated with warm compresses, diphenhydramine, and hydrocortisone cream. One of 18 patients developed a grade II general urticaria, and amifostine was discontinued. Four of 18 patients experienced treatment breaks due to hypotension, with one patient discontinued from treatment with amifostine. All cases of hypotension appeared to be related to the disease process (dehydration) rather than to amifostine treatment. Nausea was seen in 2/10 patients who did not receive chemotherapy and in 4/8 chemoradiotherapy patients. Two of 18 patients experienced low-grade fevers, for which non-amifostine causes were documented. Conclusions: Subcutaneous administration of amifostine is generally well-tolerated and convenient. It may be a preferable route of administration when used for radioprotection.
2132
Encouraging Early Results for Advanced Stage III-IV Nasopharyngeal Carcinoma using NeoadjuvantConcurrent Chemotherapy and Accelerated Radiotherapy
A. Lee, W.M. Sze, T.K. Yau, R. Yeung, K. Chan, C. Ng Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China Purpose/Objective: To study the possibility of improving tolerance and treatment outcome for advanced nasopharyngeal carcinoma by combining concurrent chemotherapy with accelerated radiotherapy and changing non-concurrent chemotherapy to neoadjuvant sequencing. Materials/Methods: During the period January 1998 to March 2001, 40 patients (10% Stage III and 90% Stage IV by AJCC 1997 System) with loco-regional infiltration too extensively for adequate coverage by the contemporary radiotherapy technique were treated with 3 cycles of chemotherapy using Cisplatin and 5-Fluorouracil prior to commencement of radiotherapy plus another 3 cycles of Cisplatin. All were irradiated with accelerated fractionation at 2 Gy per fraction, 6 daily fractions per week, to a total of 66-70 Gy. Results: Compliance with chemotherapy: 83% of patients completed 3 cycles of neoadjuvant and 55% completed ⬎⫽2 cycles of concurrent chemotherapy. Median total dose of Cisplatin given was 510 mg/m2 (range: 200 – 600). Grade ⬎⫽3 acute toxicities attributed to chemotherapy were observed in 23% of patients during the neoadjuvant phase and 30% during the concurrent phase. All patients completed the intended course of radiotherapy and the median overall radiotherapy time was 42 days (range: 38 –50). Grade ⬎⫽3 mucositis and skin reaction were observed in 58% and 16% of patients, respectively. The median weight loss during the whole course of treatment was 9% of initial body weight. With a median follow-up of 1.7 years (range: 0.5-3.4), the 2-year actuarial overall survival was 82% and progression-free survival 81%. The corresponding local, nodal and distant failure-free rates were 90%, 100%, and 89%, respectively. Altogether 9 (23%) patients developed Grade ⬎⫽3 late radiation complications, the 2-year actuarial rate at 33%. Four of them had impairment of hearing, but none had other neurological damage. Conclusions: Changing the chemotherapy sequence to neoadjuvant-concurrent could increase the total dose of Cisplatin given, particularly during the neoadjuvant phase. The treatment was well tolerated even when combined with accelerated fractionation. The early tumor control results achieved for this most advanced group are substantially better than historic data. The current approach is a promising strategy, and confirmation of therapeutic gain by prospective randomized trial is warranted.
2133
A Population-Based Three Dimensional Atlas of the Head and Neck Lymph Nodes for Conformal (IMRT) Radiotherapy
I. Poon3, N. Fischbein2, J. Ho4, N. Lee1, P. Akazawa1, P. Xia1, T. Phillips1 1 Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, 2Department of Diagnostic Radiology, University of California, San Francisco, San Francisco, CA, 3Department of Radiation Oncology, Hamilton Regional Cancer , Hamilton, ON, Canada, 4Royal St. George’s College, Toronto, ON, Canada
287