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Full dose re-irradiation of unresectable head and neck carcinoma (HNC): A serie of 169 patients
Proceedings of the 40th A n n u a l A S T R O Meeting
1033 INTENSIFICATION OF RAD1OCItEMOTHERAI'Y WITII AMIFOSTINE IN HEAD AND NECK CANCER. J Btintzel, M Glatzel, D Fr6hlich, R Weinang, K Kfittner, Departments of ENT and Radiotherapy, Klinikum Suhl, Suhl, Germany Purpose/Objective: Amifostine, an organic thioplmsphate, has been shown to protect normal tissues from the effects ofchemo- and radiotherapy without loss of anti-tumour activity. Based on previous work (Btintzel, Blood, 1997), we explored amifostine's role in allowing intensification of a concurrent radiochemotherapy regimen. Materials & Methods: Forty-three patients, in 3 different treatment arms, received RT to a total dose of 70 Gy administered in daily fractions of 2 Gy, 5 days/week. Group A received carboplatin 70 mg/m 2 and 5-FU 600 mg/m2 administered on days 1-5 and 21-25, Group B carboplatin 70 mg/m 2 administered on days I-5, 11-15, 21-25 and 31-35 and Group C carboplatin 70 mg/m 2 administered on days 1-5 and 21-25 of treatment. All patients received amifostine at a total dose of 500 mg administered 30 minutes prior to carboplatin. No amifostine was given on days when RT was given alone. Results: A (Carb/FU/RT) B (Carb/RT/interns) C (Carb/RT) (n= 15) (n= 13) (n- 15) WHO Grade 1 2 3 4 1 2 3 4 1 2 3 4 Xerostomia 7 7 / / 8 5 / / 9 4 / / Mucositis 8 4 2 1 7 6 0 0 9 4 1 0 Anemia 2 1 0 0 2 2 0 0 1 1 0 0 Leucapenia 6 1 0 0 2 2 2 1 2 3 0 0 Thrombocytopenia 1 0 1 0 2 1 1 1 0 1 0 0 Median follow up is 18 months. The overall incidence in all treatment groups of Grade 2 xerostomia was 16/43 (37%) and Grade 3/4 mucositis 4/43 (9%), comparing favorably to the incidence of these toxicities without amifostine (80% and 50-80%, respectively). The overall response rate to treatment was 91% with no differences seen between the treatment groups. Conclusion: The use of amifostine allows intensive radiochemotherapy regimens while maintaining a high response rate to treatment in patients with head and neck cancer.
1034 FULL DOSE RE-IRRADIATION OF UNRESECTABLE HEAD AND NECK CARCINOMA (HNC) : A SERIE OF 169 PATIENTS
R de Crevoisier, J Bourhis, C Domenge, P Wibault, A Lusinchi, G Mamelle, G Schwaab, P Marandas, JP Armand, B Luboinski, F Eschwege. Institut Gustave Roussy, Villejuif, 94805. France Purpose/Objective : To review our experience using full-dose external re-irradiation given with a curative intent in patients with unresectable I-INC.
Materials & Methods : Between January 1980 and December 1996, 169 patients presenting with unresectable non metastatic HNC in a previously irradiated area (median previous total dose = 60 Gy) were re-irradiated using 3 different modalities : 1) radiotherapy alone (65 Gy/6,5 weeks), 2 Gy/day) (N-27), 2) 5 to 6 cycles of radiotherapy (2 Gy/d, day 1 to 5) with simultaneous 5-FU (800 mg/mVd, Day 1 to 5) and hydroxyurea (1,5g/d, day 1 to 5) (median total dose=60 Gy) (N=I06) (= ~ Vokes protocol ,~), 3) bifractionated radiotherapy (1,5 Gy x 2/d, median total dose = 60 Gy) with concomitant mitomycin C, 5-FU and cisplatin (N=36). Histology were SCC for 85% of tumors, UCNT for 14% and adenocarcinoma for 1%. Tumors were local recurrences for 44%, nodal recurrences for 23%, local and nodal recurrences for 14% and 19% for second primary. The median time between the first and the second irradiation was 33 months. The median total cumulative doses of the 2 irradiations was 120 Gy. A spinal cord exclusion was systematicaly performed for the second irradiation and the median intersection volume of the 2 irradiation was 580 cm3. The median follow-up of the study was 70 months. Results : 1) Acute toxicity : mucositis (Gr. 3 and 4 0 M S ) : 32% and 14%, dermatitis (Gr. 3 0 M S ) : 9%, hand ad foot syndrome : 17% (using 5FU) and neutropenia and thrombocytopenia (Gr. 3 and 4 0 M S ) : 4 patients. 2) Late toxicity (> 6 months) : cervical fibrosis (Gr. 2-3 RTOG) : 41%, mucosal necrosis : 21%, osteoradionecrosis : 8% and trismus : 30%. In addition, 5 patients died of carotid haemorrhage, apparently in complete remission. 3) Tumor response and survival : Complete response evaluated 6 months after the onset of reirradiation was 37%. Overall survival (Kaplan-Meier) at 2 and 5 years were 21 and 9% respectively. The patterns of failure were local only for 53% of patients, nodal only for 20%, metastatic only for 7%, local and nodal for 8% and locoregional and metastatic for 12%. Overall median survival was 10 months for the entire population. 13 patients were found to be long term survivors and free of disease, and all but 1 were treated in the ~ Vokes protocol ,. Conclusion : Full-dose of reirradiation was feasible in patients with inoperable HNC. Adverse events still remain acceptable, even though the incidence and severity of late toxicity seemed to be markedly increased in comparison with that observed after the first irradiation. The data strongly suggest that survival seemed potentially better than that generally obtained using palliative chemotherapy alone.
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1033 INTENSIFICATION OF RAD1OCItEMOTHERAI'Y WITII AMIFOSTINE IN HEAD AND NECK CANCER. J Btintzel, M Glatzel, D Fr6hlich, R Weinang, K Kfittner, Departments of ENT and Radiotherapy, Klinikum Suhl, Suhl, Germany Purpose/Objective: Amifostine, an organic thioplmsphate, has been shown to protect normal tissues from the effects ofchemo- and radiotherapy without loss of anti-tumour activity. Based on previous work (Btintzel, Blood, 1997), we explored amifostine's role in allowing intensification of a concurrent radiochemotherapy regimen. Materials & Methods: Forty-three patients, in 3 different treatment arms, received RT to a total dose of 70 Gy administered in daily fractions of 2 Gy, 5 days/week. Group A received carboplatin 70 mg/m 2 and 5-FU 600 mg/m2 administered on days 1-5 and 21-25, Group B carboplatin 70 mg/m 2 administered on days I-5, 11-15, 21-25 and 31-35 and Group C carboplatin 70 mg/m 2 administered on days 1-5 and 21-25 of treatment. All patients received amifostine at a total dose of 500 mg administered 30 minutes prior to carboplatin. No amifostine was given on days when RT was given alone. Results: A (Carb/FU/RT) B (Carb/RT/interns) C (Carb/RT) (n= 15) (n= 13) (n- 15) WHO Grade 1 2 3 4 1 2 3 4 1 2 3 4 Xerostomia 7 7 / / 8 5 / / 9 4 / / Mucositis 8 4 2 1 7 6 0 0 9 4 1 0 Anemia 2 1 0 0 2 2 0 0 1 1 0 0 Leucapenia 6 1 0 0 2 2 2 1 2 3 0 0 Thrombocytopenia 1 0 1 0 2 1 1 1 0 1 0 0 Median follow up is 18 months. The overall incidence in all treatment groups of Grade 2 xerostomia was 16/43 (37%) and Grade 3/4 mucositis 4/43 (9%), comparing favorably to the incidence of these toxicities without amifostine (80% and 50-80%, respectively). The overall response rate to treatment was 91% with no differences seen between the treatment groups. Conclusion: The use of amifostine allows intensive radiochemotherapy regimens while maintaining a high response rate to treatment in patients with head and neck cancer.
1034 FULL DOSE RE-IRRADIATION OF UNRESECTABLE HEAD AND NECK CARCINOMA (HNC) : A SERIE OF 169 PATIENTS
R de Crevoisier, J Bourhis, C Domenge, P Wibault, A Lusinchi, G Mamelle, G Schwaab, P Marandas, JP Armand, B Luboinski, F Eschwege. Institut Gustave Roussy, Villejuif, 94805. France Purpose/Objective : To review our experience using full-dose external re-irradiation given with a curative intent in patients with unresectable I-INC.
Materials & Methods : Between January 1980 and December 1996, 169 patients presenting with unresectable non metastatic HNC in a previously irradiated area (median previous total dose = 60 Gy) were re-irradiated using 3 different modalities : 1) radiotherapy alone (65 Gy/6,5 weeks), 2 Gy/day) (N-27), 2) 5 to 6 cycles of radiotherapy (2 Gy/d, day 1 to 5) with simultaneous 5-FU (800 mg/mVd, Day 1 to 5) and hydroxyurea (1,5g/d, day 1 to 5) (median total dose=60 Gy) (N=I06) (= ~ Vokes protocol ,~), 3) bifractionated radiotherapy (1,5 Gy x 2/d, median total dose = 60 Gy) with concomitant mitomycin C, 5-FU and cisplatin (N=36). Histology were SCC for 85% of tumors, UCNT for 14% and adenocarcinoma for 1%. Tumors were local recurrences for 44%, nodal recurrences for 23%, local and nodal recurrences for 14% and 19% for second primary. The median time between the first and the second irradiation was 33 months. The median total cumulative doses of the 2 irradiations was 120 Gy. A spinal cord exclusion was systematicaly performed for the second irradiation and the median intersection volume of the 2 irradiation was 580 cm3. The median follow-up of the study was 70 months. Results : 1) Acute toxicity : mucositis (Gr. 3 and 4 0 M S ) : 32% and 14%, dermatitis (Gr. 3 0 M S ) : 9%, hand ad foot syndrome : 17% (using 5FU) and neutropenia and thrombocytopenia (Gr. 3 and 4 0 M S ) : 4 patients. 2) Late toxicity (> 6 months) : cervical fibrosis (Gr. 2-3 RTOG) : 41%, mucosal necrosis : 21%, osteoradionecrosis : 8% and trismus : 30%. In addition, 5 patients died of carotid haemorrhage, apparently in complete remission. 3) Tumor response and survival : Complete response evaluated 6 months after the onset of reirradiation was 37%. Overall survival (Kaplan-Meier) at 2 and 5 years were 21 and 9% respectively. The patterns of failure were local only for 53% of patients, nodal only for 20%, metastatic only for 7%, local and nodal for 8% and locoregional and metastatic for 12%. Overall median survival was 10 months for the entire population. 13 patients were found to be long term survivors and free of disease, and all but 1 were treated in the ~ Vokes protocol ,. Conclusion : Full-dose of reirradiation was feasible in patients with inoperable HNC. Adverse events still remain acceptable, even though the incidence and severity of late toxicity seemed to be markedly increased in comparison with that observed after the first irradiation. The data strongly suggest that survival seemed potentially better than that generally obtained using palliative chemotherapy alone.
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