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2144 Broncho-pulmonary toxicity in stage III non small cell lung cancer patients treated with taxol containing chemotherapy and concurrent preoperative or definitive radiation therapy
312
1. J. Radiation
Oncology*Biology*Physics
Volume
39, Number
2, Supplement,
1997
2143 DAILY ETOPOSIDE AND CISPLATIN DURING THORACIC ADVANCED NON-SMALL CELL LUNG CANCER J.A. Bonner, Mayo Clinic
S. Frytak, J. Sloan, R.L. Foote, R.S. Marks, and Mayo Foundation, Rochester, MN
RADIOTHERAPY
E.T. Creagan,
FOR PATIENTS
R.L. Richardson,
WITH
LOCALLY
C. Deschamps
Purpose: A phase I/II trial was performed to investigate the toxicity and potential efficacy of delivering two radiosensitizing chemotherapeutic agents (cisplatin and etoposide) on a daily basis during twice daily thoracic radiotherapy for patients with locally advanced non-small cell lung cancer. Methods: Patients were eligible for this trial if they had unresectable or incompletely resected biopsy-proven stage IIIA or IIIB non-small cell lung carcinoma. However, patients with contralateral hilar or supraclavicular disease were excluded. Patients were required to have an ECOG performance status of O-2 and 110% weight loss during the preceding three months. Thoracic radiation treatment (TRT) was delivered as accelerated hyperfractionated TRT with 150 cGy given twice daily beginning on a Monday. Patients received a two-week break between two courses of 3000 cGy (total dose:600OcGy). Patients received etoposide (25 mg/m2 po) on days I-12 and cisplatin (3 mg/m2 IV) on days l-5 and 8-12 of each course of TRT. Two weeks following the completion of TRT patients began two cycles (q 28d) of etoposide (25 mg/m2, PO, dl-21) and cisplatin (50 mg/m2 IV, dl). Patients were seen in followup at 2 months following the completion of therapy and subsequently at 3 month intervals for the first year. Results: Seventeen patients were entered on the trial and the median followup was 11 months. Of the 17 patients, 13 had evaluable disease and 4 had measurable disease; 16 were deemed unresectable and one had an incomplete resection; 6 had squamous cell carcinomas and 11 had non-squamous cell carcinomas; 5 had primary tumors greater than 6 cm, 9 were 3-6 cm and 3 were <3 cm; 14 had less than 5% weight loss and 3 had 5-101 weight loss; 9 bad stage IIIA disease and 8 had IIIB disease. The most common hematologic toxicity was leukopenias: 4 patients had grade 3 and 1 had grade 4 toxicity. No grade 3 or greater thrombocytopenia was observed. There were 6 grade 3 nonhematologic toxicities, one incident each of alopecia , anorexia, skin , lethargy , esophagitis and dyspnea. No grade 4 or 5 non-hematologic toxicities were reported. The median time to progression was 8.8 months and the freedom from progression rates at 1 and 2 years were 45% and 22% respectively. The median survival was 19.8 months and the survival rates at 1 and 2 years were 70% and 35%. respectively. Conclusion:
These results are encouraging
Acknowledgments:
and suggest that this regimen
The authors would like to acknowledge
warrants
further
the gift of oral etoposide
study.
capsules from Bristol-Myers
.
2144 BRONCHO-PULMONARY CONTAINING Sharma, Suzanne,
TOXICITY CHEMOTHERAPY
IN STAGE Ill NON AND CONCURRENT
M. Maddie, M.D., Gupta-Burt, Shalina. M.D., Lincoln, Sarah T., M.D., Bonomi,
Purpose/Objective: radiation as preoperative
The objective or definitive
of this trial treatment
SMALL CELL LUNG PREOPERATIVE
M.D., Recine, Diane C., Faber, Philip D.. M.D., Rush-Presbyterian
CANCER PATIENTS TREATED WITH TAXOL OR DEFINITIVE RADIATION THERAPY
L. Penfield, M.D., Warren, William H., M.D., LaFollette, St. Luke’s Medical Center. Chicago, IL
was to test the feasibility of taxol containing combination for stage Ill non small cell lung cancer patients.
chemotherapy
and
concurrent
Methods and Materials: Thirty-three patients were treated on this trial. The initial regimen was (Group 1 pts.): paraplatin (P) (AUC of 4) on day 2, etoposide (E) 50 mg po days 1-5 and 8-12, cisplatin (C) 50 mg/m2 on day 21 and taxol (T) 35 mg/m2 escalated to 45 mg/m2 on days 1 and 8, 24 hr. infusion. After treatment of 10 pts., the regimen was modified as follows (Group 2 pts.): P (AUC of 4) on day 1, E 40 mglm2 IV daily and days 2-5, and T 80 mg/m2 escalated to 120 mglm2 on day 1, 3 hr. infusion. After the next 16 pts., the regimen was modified again as follows (Group 3 pts.): P (AUC of 4) on day 1 and T 120 mglm2 escalated to 140 mg/m2 on day 1, 3 hr. infusion. Seven patients were treated on the latest version of the regimen for a total of 33 pts. The radiation given was uniform throughout the 3 groups. A dose of 4000 cGy in 20 fxs was given in the surgical arm and 6000 cGy in 30 fxs in the non surgical arm. Treatments were given at 200 cGy/fx. once a day, on a 2 weeks on, 2 weeks off basis. The RTOG Acute Radiation Morbidity Scoring Criteria was used to grade pneumonitis. Post-operative complications were defined as occuring early (less than or equal to 30 days) or late (greater than 30 days) following surgery. Results: Sixteen of the 33 patients went to surgery. Grade 3 radiation pneumonitis were no episodes of Grade 4 pneumonitis. Grade 3 pneumonitis occured in: One Group 2 (RT dose 4000 cGy and 6000 cGy. respectively), and 1 pt in Group complications occured in 6 of the 16 patients (37.5%) who went to surgery. In secondary to a significant drop in diffusion capacity. without radiographic evidence developed broncho-pleural fistula, 1 pt. developed pulmonary hypertension, and 1 non operated lung, requiring a 30 day hospitalization. In Group 3, 1 pt. developed (adult respiratory distress syndrome). Overall, there was 1 treatment related death. 33 patients (1 pt. had both radiation pneumonitis and then later developed pulmonary
developed in 4 of the 33 patients (12%). There patient in Group 1, (RT dose 5800 cGy). 2 pts in 3 (RT dose 6000 cGy). Major post-operative Group 1, 1 pt. required oxygen supplementation of radiation pneumonitis. In Group 2, 1 pt. pt. had a severe post-operative pneumonia in the broncho-pleural fistula, and 1 pt. had fatal ARDS Major broncho-pulmonary toxicity occured in 9 of hypertension), or in 27%.
Conclusion: The incidence of broncho-pulmonary complications in this taxol containing regimen appears to be higher than in our previous trials with concurrent chemo and radiation therapy. These findings were unpredictable and occured across the various regimens, therefore did not seem related to taxol dose or infusion time. Also radiation pneumonitis was not related to volume treated, and occured at both dose levels. Based on our observations, our future trials will involve sequential taxol containing chemotherapy followed by surgery in stage llla pts. and radiation in stage lllb pts.
1. J. Radiation
Oncology*Biology*Physics
Volume
39, Number
2, Supplement,
1997
2143 DAILY ETOPOSIDE AND CISPLATIN DURING THORACIC ADVANCED NON-SMALL CELL LUNG CANCER J.A. Bonner, Mayo Clinic
S. Frytak, J. Sloan, R.L. Foote, R.S. Marks, and Mayo Foundation, Rochester, MN
RADIOTHERAPY
E.T. Creagan,
FOR PATIENTS
R.L. Richardson,
WITH
LOCALLY
C. Deschamps
Purpose: A phase I/II trial was performed to investigate the toxicity and potential efficacy of delivering two radiosensitizing chemotherapeutic agents (cisplatin and etoposide) on a daily basis during twice daily thoracic radiotherapy for patients with locally advanced non-small cell lung cancer. Methods: Patients were eligible for this trial if they had unresectable or incompletely resected biopsy-proven stage IIIA or IIIB non-small cell lung carcinoma. However, patients with contralateral hilar or supraclavicular disease were excluded. Patients were required to have an ECOG performance status of O-2 and 110% weight loss during the preceding three months. Thoracic radiation treatment (TRT) was delivered as accelerated hyperfractionated TRT with 150 cGy given twice daily beginning on a Monday. Patients received a two-week break between two courses of 3000 cGy (total dose:600OcGy). Patients received etoposide (25 mg/m2 po) on days I-12 and cisplatin (3 mg/m2 IV) on days l-5 and 8-12 of each course of TRT. Two weeks following the completion of TRT patients began two cycles (q 28d) of etoposide (25 mg/m2, PO, dl-21) and cisplatin (50 mg/m2 IV, dl). Patients were seen in followup at 2 months following the completion of therapy and subsequently at 3 month intervals for the first year. Results: Seventeen patients were entered on the trial and the median followup was 11 months. Of the 17 patients, 13 had evaluable disease and 4 had measurable disease; 16 were deemed unresectable and one had an incomplete resection; 6 had squamous cell carcinomas and 11 had non-squamous cell carcinomas; 5 had primary tumors greater than 6 cm, 9 were 3-6 cm and 3 were <3 cm; 14 had less than 5% weight loss and 3 had 5-101 weight loss; 9 bad stage IIIA disease and 8 had IIIB disease. The most common hematologic toxicity was leukopenias: 4 patients had grade 3 and 1 had grade 4 toxicity. No grade 3 or greater thrombocytopenia was observed. There were 6 grade 3 nonhematologic toxicities, one incident each of alopecia , anorexia, skin , lethargy , esophagitis and dyspnea. No grade 4 or 5 non-hematologic toxicities were reported. The median time to progression was 8.8 months and the freedom from progression rates at 1 and 2 years were 45% and 22% respectively. The median survival was 19.8 months and the survival rates at 1 and 2 years were 70% and 35%. respectively. Conclusion:
These results are encouraging
Acknowledgments:
and suggest that this regimen
The authors would like to acknowledge
warrants
further
the gift of oral etoposide
study.
capsules from Bristol-Myers
.
2144 BRONCHO-PULMONARY CONTAINING Sharma, Suzanne,
TOXICITY CHEMOTHERAPY
IN STAGE Ill NON AND CONCURRENT
M. Maddie, M.D., Gupta-Burt, Shalina. M.D., Lincoln, Sarah T., M.D., Bonomi,
Purpose/Objective: radiation as preoperative
The objective or definitive
of this trial treatment
SMALL CELL LUNG PREOPERATIVE
M.D., Recine, Diane C., Faber, Philip D.. M.D., Rush-Presbyterian
CANCER PATIENTS TREATED WITH TAXOL OR DEFINITIVE RADIATION THERAPY
L. Penfield, M.D., Warren, William H., M.D., LaFollette, St. Luke’s Medical Center. Chicago, IL
was to test the feasibility of taxol containing combination for stage Ill non small cell lung cancer patients.
chemotherapy
and
concurrent
Methods and Materials: Thirty-three patients were treated on this trial. The initial regimen was (Group 1 pts.): paraplatin (P) (AUC of 4) on day 2, etoposide (E) 50 mg po days 1-5 and 8-12, cisplatin (C) 50 mg/m2 on day 21 and taxol (T) 35 mg/m2 escalated to 45 mg/m2 on days 1 and 8, 24 hr. infusion. After treatment of 10 pts., the regimen was modified as follows (Group 2 pts.): P (AUC of 4) on day 1, E 40 mglm2 IV daily and days 2-5, and T 80 mg/m2 escalated to 120 mglm2 on day 1, 3 hr. infusion. After the next 16 pts., the regimen was modified again as follows (Group 3 pts.): P (AUC of 4) on day 1 and T 120 mglm2 escalated to 140 mg/m2 on day 1, 3 hr. infusion. Seven patients were treated on the latest version of the regimen for a total of 33 pts. The radiation given was uniform throughout the 3 groups. A dose of 4000 cGy in 20 fxs was given in the surgical arm and 6000 cGy in 30 fxs in the non surgical arm. Treatments were given at 200 cGy/fx. once a day, on a 2 weeks on, 2 weeks off basis. The RTOG Acute Radiation Morbidity Scoring Criteria was used to grade pneumonitis. Post-operative complications were defined as occuring early (less than or equal to 30 days) or late (greater than 30 days) following surgery. Results: Sixteen of the 33 patients went to surgery. Grade 3 radiation pneumonitis were no episodes of Grade 4 pneumonitis. Grade 3 pneumonitis occured in: One Group 2 (RT dose 4000 cGy and 6000 cGy. respectively), and 1 pt in Group complications occured in 6 of the 16 patients (37.5%) who went to surgery. In secondary to a significant drop in diffusion capacity. without radiographic evidence developed broncho-pleural fistula, 1 pt. developed pulmonary hypertension, and 1 non operated lung, requiring a 30 day hospitalization. In Group 3, 1 pt. developed (adult respiratory distress syndrome). Overall, there was 1 treatment related death. 33 patients (1 pt. had both radiation pneumonitis and then later developed pulmonary
developed in 4 of the 33 patients (12%). There patient in Group 1, (RT dose 5800 cGy). 2 pts in 3 (RT dose 6000 cGy). Major post-operative Group 1, 1 pt. required oxygen supplementation of radiation pneumonitis. In Group 2, 1 pt. pt. had a severe post-operative pneumonia in the broncho-pleural fistula, and 1 pt. had fatal ARDS Major broncho-pulmonary toxicity occured in 9 of hypertension), or in 27%.
Conclusion: The incidence of broncho-pulmonary complications in this taxol containing regimen appears to be higher than in our previous trials with concurrent chemo and radiation therapy. These findings were unpredictable and occured across the various regimens, therefore did not seem related to taxol dose or infusion time. Also radiation pneumonitis was not related to volume treated, and occured at both dose levels. Based on our observations, our future trials will involve sequential taxol containing chemotherapy followed by surgery in stage llla pts. and radiation in stage lllb pts.