- Email: [email protected]
radiotherapy for stage III non-small cell lung cancer (NSCLC)
63 surable primary therapy.
tumor;
no CNS involvement;
no previous
chemo-
or radio-
Preliminary Results: 138 pts entered by 30 centers and treated with ~13 different Cisplatin-based chemotherapy regimens. 95 pts are evaluable, 63 (66%) achieved a major response (CR 11% and PR 55%). 13 pts (14%) had PD, 16 pts (17%) SD and 3 pts stopped chemotherapy because of grade 4 leucopenia, toxic death, and neuropathy respectively. .61 pts have been randomized, 31 to surgery and 30 to radiotherapy. 1 pt refused randomization. Of only 15 surgery pts and 7 radiotherapy pts data are now available. Of the 15 surgery pts 13 had a radical resection and 1 pt died due to a postoperative complication. Conclusions: a large multicentre trial of combined modality in stage llla (N2) NSCLC seems to be feasible with a high response rate to neoadjuvant chemotherapy and a high resection rate. Complete data on 140 pts will be presented.
I240
Multimodality Preoperative involvement
therapy for stage Ill thymoma: radiotherapy (RT) for patients of major vessels or lung
with
M. Myojin, N.C. Choi, D.J. Mathisen, J.C. Wain, C.D. Wright, E.B. Hug, R.W. Carey, N.L. Harris, D. Finklestein, H.C. Grille. Massachusetts Genera/ Hospital, Harvard Medical School, Boston, MA, USA Stage Ill thymoma still carries a 5-year survival rate of 50%. The objective of this study was to evaluate the pattern of failure and therapy outcome according to the initial treatment plan, and search for a new direction. Between 1975 and 1993, 111 patients with thymoma were treated at Massachusetts General Hospital. Of these, 32 patients were found to have stage Ill thymoma. The initial treatment plans included surgery (S) + Postop RT in 21, Preop RT + S 6, S alone 2 and chemotherapy (CT) combined (CT + S + RT or S + CT + RT) 3 patients. Surgical procedure consisted of thymectomy plus resection of pericardium, pleura or lung as it was deemed indicated. Postop RT delivered 45 to 50 Gy/25 fractions (F)/5 weeks. Preop RT delivered 40 Gy/20 F/4 weeks in the earlier study period; this schedule was modified to a 21-27 Gy in 1.5 Gy/F, twice daily, 5 days/week. Patients with stage Ill thymoma accounted for 29% (32 patients) of all patients. Median age was 57 years (range 27-81) and male to female ratio 10:22. The median follow-up time was 71 months. The overall sutvival rates were 71% and 48% at 5 and 10 years respectively. Survival rates at 5 and 10 years for the subgroups were 66% and 39% vs. 100% & 67% for S + Postop RT vs. Preop RT + S respectively, p = 0.05 (G. Wilcoxon). Causes of failure included recurrent thymoma in 71% (10/14), surgery related mortality in 21% (3/14), and other 7% (l/14). Preop RT group had one failure (l/6) at the tumor bed. Failure in the pleura and lung, that accounted for 67% (8/12) of all recurrences, came from S + Postop RT or S alone group. Preop RT may be able to reduce pleural/lung recurrence, operative mortality, and result in improved survival in stage III thymoma.
Wednesday, 13 August 1997 ORAL
10:30-12:00
SESSION
Combined Modality Therapy
j241*I Phase
VII trial of neoadjuvant chemo/radiotherapy for stage cancer (NSCLC)
H.B. Niell, A.A. Miller, P. Kumar, J.P. Griffin. TN 38 104, USA
and concomitant Ill non-small cell VA Medical
Center,
lung
Memphis
This trial was designed to define the maximum tolerable doses (MTD) of neoadjuvant and concomitant cisplatin and paclitaxel with radiation therapy in stage Ill NSCLC. Inclusion criteria: performance status O-2; stage llla
or lllb disease; no prior chemotherapy or radiation therapy. Neoadjuvant therapy consisted of TAX (1 hr) from 150-250 mg/m2 with DDP at 100 mg/m2 every 3 weeks for 2 courses. Planned delayed thoracic radiotherapy (TRT) (Day 43) was delivered at 2 Gy/fx to the primary tumor and overt nodal disease. Initial radiation volume treated the pre-chemo extent of disease to include the primary tumor bed, overt nodal disease and the mediastinum to 40 Gy followed by a 20 Gy boost to the primary tumor and gross lymphadenopathy. 21 patients underwent the TRT (1 refused) and 17 completed therapy. The median total TRT dose was 60 Gy (range = 24-68 Gy). Only 5 patients experienced more than a l-week interruption of TRT due to toxicity. Acute grade Ill or higher TRT toxicity was as follows: grade III esophagitis = 4, grade Ill dehydration = 1, grade III radioepidermititis = 1. Concomitant chemo consisting of TAX 40 mg/m* (1 hr) and 30 mg/m2 of DDP was given weekly during TRT. 25 patients have entered the study, 10 with stage llla and 15 with Illb. There were 13 squamous, 2 adenocarcinomas, and 10 large cell lung cancers. Level
# Pts
TAX
DDP
Hem-DLT
1 2 3 4 5 6 7
6 3 3 4 3 3 3
150 165 175 185 200 225 250
100 100 100 100 100 100 100
2 0
Non-Hem-DLT
1 renal 0 0 0 1 renal/l neuro
Combined modality therapy resulted in 3 patients experiencing grade 3 neutropenia and 3 grade 3 esophagitis. Of 22 evaluable patients, 13 (59%) obtained a PR to neoadjuvant therapy. The projected MTD is 225 mg/m2 of taxol. This combination regimen has substantial activity with manageable toxicity in patients with stage Ill NSCLC.
242 L-T
Promising long term outcome of weekly paclitaxel and carboplatin with simultaneous thoracic radiotherapy (TRT) for locally advanced non-small cell lung cancer (NSCLC)
C.P. Belani, J. Aisner, R. Day, R. Ramanathan, J. Jett, M.J. Capozzoli, S. Bahri, D. Hiponia. University of Pittsburgh Cancer Institute, Pittsburgh, PA and University of Maryland Cancer Center. Bakimore, MD, USA Paclitaxel and carboplatin have demonstrated prominent activity in NSCLC. Paclitaxel also has favorable interactions with platinum compounds and potentiates the effects of ionizing radiation in low concentrations. In this phase II study, we combined weekly low dose paclitaxel at 45 mg/m’ (3-hour infusion) with weekly carboplatin 100 mgIm2 and simultaneous standard-dose thoracic radiotherapy for patients with locally advanced NSCLC. The TRT was given in 1.8 Gy fractions, five times a week for 6-7 weeks, to a total of 60-65 Gy. Thirty-eight patients (pts.) were entered. Patient characteristics include: ECOG performance status 0 (24 pts.) or 1 (14 pts.); histology - 15 squamous cell carcinoma, 17 adenocarcinoma, 2 large cell carcinoma, and 4 poorly differentiated NSCLC; median age 64 years (32-79); clinical stage llla 16 pts., stage lllb 22 pts. The salient grade 3/4 toxicities included: 9 grade 3 leucopenia, 3 grade 3 mucositis and esophagitis, 2 grade 3 fatigue and 2 grade 3 nausea/vomiting. Overall the regimen was well tolerated. There were 12 instances of dose reduction and there was a delay in treatment duration of 11 week in 5 patients. Three patients died as a result of rapidly progressive disease without any evidence of dose-limiting toxicities. The median survival has not yet been reached. The 1 year, 2 year and 3 year actuarial survival rates for this group of patients with locally advanced NSCLC are 63% (95 Cl: 44-77%), 54% (95 Cl:35-70%), and 54% (95 Cl: 35-70%) respectively. In conclusion: The regimen of weekly paclitaxel and carboplatin with simultaneous thoracic radiotherapy is active and shows promising long-term results in locally advanced NSCLC.
tumor;
no CNS involvement;
no previous
chemo-
or radio-
Preliminary Results: 138 pts entered by 30 centers and treated with ~13 different Cisplatin-based chemotherapy regimens. 95 pts are evaluable, 63 (66%) achieved a major response (CR 11% and PR 55%). 13 pts (14%) had PD, 16 pts (17%) SD and 3 pts stopped chemotherapy because of grade 4 leucopenia, toxic death, and neuropathy respectively. .61 pts have been randomized, 31 to surgery and 30 to radiotherapy. 1 pt refused randomization. Of only 15 surgery pts and 7 radiotherapy pts data are now available. Of the 15 surgery pts 13 had a radical resection and 1 pt died due to a postoperative complication. Conclusions: a large multicentre trial of combined modality in stage llla (N2) NSCLC seems to be feasible with a high response rate to neoadjuvant chemotherapy and a high resection rate. Complete data on 140 pts will be presented.
I240
Multimodality Preoperative involvement
therapy for stage Ill thymoma: radiotherapy (RT) for patients of major vessels or lung
with
M. Myojin, N.C. Choi, D.J. Mathisen, J.C. Wain, C.D. Wright, E.B. Hug, R.W. Carey, N.L. Harris, D. Finklestein, H.C. Grille. Massachusetts Genera/ Hospital, Harvard Medical School, Boston, MA, USA Stage Ill thymoma still carries a 5-year survival rate of 50%. The objective of this study was to evaluate the pattern of failure and therapy outcome according to the initial treatment plan, and search for a new direction. Between 1975 and 1993, 111 patients with thymoma were treated at Massachusetts General Hospital. Of these, 32 patients were found to have stage Ill thymoma. The initial treatment plans included surgery (S) + Postop RT in 21, Preop RT + S 6, S alone 2 and chemotherapy (CT) combined (CT + S + RT or S + CT + RT) 3 patients. Surgical procedure consisted of thymectomy plus resection of pericardium, pleura or lung as it was deemed indicated. Postop RT delivered 45 to 50 Gy/25 fractions (F)/5 weeks. Preop RT delivered 40 Gy/20 F/4 weeks in the earlier study period; this schedule was modified to a 21-27 Gy in 1.5 Gy/F, twice daily, 5 days/week. Patients with stage Ill thymoma accounted for 29% (32 patients) of all patients. Median age was 57 years (range 27-81) and male to female ratio 10:22. The median follow-up time was 71 months. The overall sutvival rates were 71% and 48% at 5 and 10 years respectively. Survival rates at 5 and 10 years for the subgroups were 66% and 39% vs. 100% & 67% for S + Postop RT vs. Preop RT + S respectively, p = 0.05 (G. Wilcoxon). Causes of failure included recurrent thymoma in 71% (10/14), surgery related mortality in 21% (3/14), and other 7% (l/14). Preop RT group had one failure (l/6) at the tumor bed. Failure in the pleura and lung, that accounted for 67% (8/12) of all recurrences, came from S + Postop RT or S alone group. Preop RT may be able to reduce pleural/lung recurrence, operative mortality, and result in improved survival in stage III thymoma.
Wednesday, 13 August 1997 ORAL
10:30-12:00
SESSION
Combined Modality Therapy
j241*I Phase
VII trial of neoadjuvant chemo/radiotherapy for stage cancer (NSCLC)
H.B. Niell, A.A. Miller, P. Kumar, J.P. Griffin. TN 38 104, USA
and concomitant Ill non-small cell VA Medical
Center,
lung
Memphis
This trial was designed to define the maximum tolerable doses (MTD) of neoadjuvant and concomitant cisplatin and paclitaxel with radiation therapy in stage Ill NSCLC. Inclusion criteria: performance status O-2; stage llla
or lllb disease; no prior chemotherapy or radiation therapy. Neoadjuvant therapy consisted of TAX (1 hr) from 150-250 mg/m2 with DDP at 100 mg/m2 every 3 weeks for 2 courses. Planned delayed thoracic radiotherapy (TRT) (Day 43) was delivered at 2 Gy/fx to the primary tumor and overt nodal disease. Initial radiation volume treated the pre-chemo extent of disease to include the primary tumor bed, overt nodal disease and the mediastinum to 40 Gy followed by a 20 Gy boost to the primary tumor and gross lymphadenopathy. 21 patients underwent the TRT (1 refused) and 17 completed therapy. The median total TRT dose was 60 Gy (range = 24-68 Gy). Only 5 patients experienced more than a l-week interruption of TRT due to toxicity. Acute grade Ill or higher TRT toxicity was as follows: grade III esophagitis = 4, grade Ill dehydration = 1, grade III radioepidermititis = 1. Concomitant chemo consisting of TAX 40 mg/m* (1 hr) and 30 mg/m2 of DDP was given weekly during TRT. 25 patients have entered the study, 10 with stage llla and 15 with Illb. There were 13 squamous, 2 adenocarcinomas, and 10 large cell lung cancers. Level
# Pts
TAX
DDP
Hem-DLT
1 2 3 4 5 6 7
6 3 3 4 3 3 3
150 165 175 185 200 225 250
100 100 100 100 100 100 100
2 0
Non-Hem-DLT
1 renal 0 0 0 1 renal/l neuro
Combined modality therapy resulted in 3 patients experiencing grade 3 neutropenia and 3 grade 3 esophagitis. Of 22 evaluable patients, 13 (59%) obtained a PR to neoadjuvant therapy. The projected MTD is 225 mg/m2 of taxol. This combination regimen has substantial activity with manageable toxicity in patients with stage Ill NSCLC.
242 L-T
Promising long term outcome of weekly paclitaxel and carboplatin with simultaneous thoracic radiotherapy (TRT) for locally advanced non-small cell lung cancer (NSCLC)
C.P. Belani, J. Aisner, R. Day, R. Ramanathan, J. Jett, M.J. Capozzoli, S. Bahri, D. Hiponia. University of Pittsburgh Cancer Institute, Pittsburgh, PA and University of Maryland Cancer Center. Bakimore, MD, USA Paclitaxel and carboplatin have demonstrated prominent activity in NSCLC. Paclitaxel also has favorable interactions with platinum compounds and potentiates the effects of ionizing radiation in low concentrations. In this phase II study, we combined weekly low dose paclitaxel at 45 mg/m’ (3-hour infusion) with weekly carboplatin 100 mgIm2 and simultaneous standard-dose thoracic radiotherapy for patients with locally advanced NSCLC. The TRT was given in 1.8 Gy fractions, five times a week for 6-7 weeks, to a total of 60-65 Gy. Thirty-eight patients (pts.) were entered. Patient characteristics include: ECOG performance status 0 (24 pts.) or 1 (14 pts.); histology - 15 squamous cell carcinoma, 17 adenocarcinoma, 2 large cell carcinoma, and 4 poorly differentiated NSCLC; median age 64 years (32-79); clinical stage llla 16 pts., stage lllb 22 pts. The salient grade 3/4 toxicities included: 9 grade 3 leucopenia, 3 grade 3 mucositis and esophagitis, 2 grade 3 fatigue and 2 grade 3 nausea/vomiting. Overall the regimen was well tolerated. There were 12 instances of dose reduction and there was a delay in treatment duration of 11 week in 5 patients. Three patients died as a result of rapidly progressive disease without any evidence of dose-limiting toxicities. The median survival has not yet been reached. The 1 year, 2 year and 3 year actuarial survival rates for this group of patients with locally advanced NSCLC are 63% (95 Cl: 44-77%), 54% (95 Cl:35-70%), and 54% (95 Cl: 35-70%) respectively. In conclusion: The regimen of weekly paclitaxel and carboplatin with simultaneous thoracic radiotherapy is active and shows promising long-term results in locally advanced NSCLC.