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351 Combined treatment of inoperable non-small cell lung cancer (NSCLC): Brachy-, teleradio-, chemo-, laser-therapy
90 1350(
Therapy - Combined Modality Induction concurrent radiochemotherapy small cell lung cancer (NSCLC)
in N2 non
P. Granone ‘, S. Margaritora r, A. Cesario ‘, P.L. Bonatti ‘, M. Balducci s, G. Mantini s, A. Turriziani *, L. Trodella s, A. Picciocchi ‘. Carbolic University of Rome, ItalK ’ Departmenf of Genera/ Surgery 1, Division of Thoracic Surgery; ‘Department of Radiology, Radiotherapy, /h/y Between January 1990 and December 1994,73 N2 NSCLC (37 llla and 36 Illb) patients received preoperative chemo-radiotherapy with a single cycle of Carboplatin (90 mg/mq/die for days 1 to 4) concurrent with radiotherapy (daily radiation dose of 180 cGy for a total dose of 5040 cGy). Two patients have been excluded from the study. When the remaining 71 patients were re-staged, 33 (46%) patients had a major clinical response (>50%), 36 (51%) had minimal response (~50%) or no change and in 2 (3%) patients there was progression of disease. Forty-four patients were judged to be resectable; 2 patients refused surgery and 10 patients could not undergo surgery due to poor respiratory function. Thirty-two patients underwent surgery (25 staged llla and 7 Illb). Thirty of the 32 operated patients were completely resected (resectability rate in patients who underwent surgery after restaging was 94%; overall resectability rate was 41%). Overall pathological downstaging rate was 60% (19/32) with 3 (10%) complete responses and 6 (20%) cases in which only microscopic neoplastic foci were found in the specimen. In the two patients who underwent explorative thoracotomy we confirmed clinical staging (T3N2; T4N2). The overall median two years suwival is 17 months with a follow up range of 2-86 months (median 23 months). There is a statistically significant difference in median survival between patients who underwent surgery - 29 months - and those who didn’t - 14 months (p = 0.0000). The actuarial survival (life table analysis) following complete resection is 45% at five years while it is 8% at 3 years and 0% at 5 years in the group who didn’t have surgery (p = 0.0000). The following conclusions are possible: preoperative radiotherapy and chemotherapy, utilizing Carboplatin, is well tolerated by patients, does not lead to postoperative complications and produces an high rate of response; there is a high resection rate for patients who respond to therapy: good long term survival have been obtained in patients with major response who underwent complete surgical resection.
I351
Combined treatment of inoperable non-small cell lung cancer (NSCLC): Brachv-, teleradio-, chemo-, laskherapy . -
V. Kolek, B. Gronych, K. Cwiertka, G. Engel. Unir Klinikum Ingolsfadt, GER, Czech Republic
of O/omouc,
CR
An optimal algorithm of the combined treatment of inoperable NSCLC doesn’t exist, but there may be some rational preferences. The present study evaluates retrospectively the mean survival (MS) after brachytherapy (BT) and teleradiotherapy (TRT) combined with chemotherapy (ChT) or lasertherapy (LT). Forty one consecutive patients (pts) with local advanced NSCLC were evaluated. The mean age of 37 men and 4 women was 57 years (40-76). Squamous carcinoma was present in 38, adenoca in 2 and giant cell ca in 1 patient. HDR BT (2 x 8 Gy lr-192) and TRT (up to 65 Gy Co-60) were applied to all patients (pts). Nine pts were treated by BT and TRT. ChT using vinorelbin, vepesid, cis- and carboplatin was given to 17 pts (in 8 prior, in 9 after BT and TRT). LT was applied in 28 pts in cases with a central critical obstruction, BT, TRT, ChT and LT was applied to 13 pts. The MS from diaqnosis was 13.5 month (ml in the total series. It was 6.3 m in BT and TR?, 16.8 m in BT, TRT and LT, 20.2 m in BT, TRT and ChT and 12.2 m in BT, TRT, ChT and LT regimen. Those with ChT had MS 14.4 m vs 12.8 m without ChT, those with LT had MS 14.7 m vs 12.2 without LT. All groups treated with radiotherapy combinated with other treatment had a longer survival that pts treated with radiotherapy alone. ChT brought a MS prolongation of 14 m, LT of 10 m, but combination of both therapies (ChT and LT) only 6 m. We conclude that larger and prospective studies on this topic are needed.
Therapy
13521 Induction chemotherapy (ICT cisplatin and vinorelbine) followed by a combination of daily irradiation and carboplatine (CBDCA) in stage IIIB non small cell lung cancer (NSCLC): Final analysis of a phase II trial E. Bardet, J.Y. Douillard, A. Riviere, E. Quoix, D. Spaeth, A. Ducolone, B. Coudert, J.L. Lagrange, P. Chomy, C. Tuchais, B. Pellae-Cosset, M. Henry-Amar. SlvdJ. Rancid, 66805 Nantes, France A phase II trial of induction CT followed by daily CBDCA and radiation was performed in order to evaluate toxicity and efficacy of such a combined modality approach. From 8/94 to l/96, 111 pts were enrolled from 8 centers. Patients population was: male 89, female 12, mean age 58, median PS = 1, 62% squamous cell. No restriction were imposed based on weight lost, supraclavicular lymph node or vena cava syndrome. ICT consisted in Cisplatin (CDDP) 120 mgIma, week 1, 5 and 9 Vinorelbine (NVB) 30 mg/ms week 1 to 9, except week 3 and 7 where dose was reduced to 15 mg/ms. Patients free of distant progression to ICT received megavoltage radiation (66 Gy, 2 Gy/fraction) preceded by 15 mg/m’ CBDCA 2 to 4 hr before radiation daily. Final evaluation was performed 3 months after the end of radiation. As of 12/01/96, 101 patients have been analysed. Received doses of NVB and CDDP were 97 and 78% of scheduled respectively. Grade 3-4 hematological toxicity occurred in 76% of patients. Five patients died before the end of ICT. Response rate was 58% (4 CR, 52 PR), 30 patients were stable, 10 failed including 3 distant progression. Six patients were rendered resectable. Combined CBDCA-radiation was delivered to 75 patients. Delivered dose of CBDCA was 94%, mean dose of radiation 66 Gy. Additional CT identical to induction was given for 2 cycles only to 28 patients, mainly due to toxicity. Response rate to the overall schedule was 52% of evaluable cases, and 35% in intent to treat. Local control at 3 months was achived in 64% evaluable patients and 47% in intent to treat. The 1 year survival rate was 44%. Overall 33 patients died from local progression, 20 from distant metastasis, 4 from treatment related complications, 8 from intercurent disease. Combined ICT followed by concomitant CBDCA-radiation appears feasible in stage IIIB NSCLC, even in an unselected patient population. Contribution of CBDCA as radiosensitizer to improve local control is presently investigated in a phase Ill trial.
I353
Combined chemoradiation therapy for locally advanced resectable non small cell lung cancer (NSCLC)
J.Y. Douillard, E. Bardet, A. Le Groumellec, B. Maury, J. Bennouna, F. Morel, P. Despins. Centre Ren6 Gauducheau 44805 Nanfes-St Herblain, France Neoadjuvant chemotherapy for stage IIIA has proven efficacious in term of survival in randomised trials. In order to possibly improve overall results other modalities have to be evaluated. From May 1995 to April 1996, 9 patients (9 male, mean age 52 y, median PS = 1, squamous cell 8, large cell 1 stage IIIA: 8, 4T2N2, 2T3N2, lT3N1, 1118: 1 T2N3) received concomitant chemoradiotherapy with Vinorelbine 25 ms/m2, lfosfamide 3 mg/m’, Cisplatin 65 mg/m* day 1 and 21 along with 40-45 Gy megavoltage radiation over 4 weeks (2 Gy/fraction, 5 fractions/week). Radical surgery was performed 4 weeks after the end of radiation. Treatment as scheduled was delivered in 8/9 patients, 1 got only one course of chemotherapy for hematotoxicity. Response rate to induction treatment was 1 CR, 5 PR, 3 STB, 0 PRO. All patients were operated on with 8/9 totally resected. One, initially IIIB had an incomplete resection. One patient was tumor free at histology, 5 showed minimal microscopic residual tumor, 3 presented with macroscopic residual disease. One patient died from sepsis within 27 days after surgery. With a median follow-up of 10 months, 6/9 are in complete remission, 1 patient died of distant progression at 6 months, one died from respiratory distress due to Bronchiolitis obliterans. Based on this limited series, combined chemoradiation seem feasable in patients with resectable locally advanced NSCLC and should be investigated in phase Ill as compared to the use of chemotherapy alone.
Therapy - Combined Modality Induction concurrent radiochemotherapy small cell lung cancer (NSCLC)
in N2 non
P. Granone ‘, S. Margaritora r, A. Cesario ‘, P.L. Bonatti ‘, M. Balducci s, G. Mantini s, A. Turriziani *, L. Trodella s, A. Picciocchi ‘. Carbolic University of Rome, ItalK ’ Departmenf of Genera/ Surgery 1, Division of Thoracic Surgery; ‘Department of Radiology, Radiotherapy, /h/y Between January 1990 and December 1994,73 N2 NSCLC (37 llla and 36 Illb) patients received preoperative chemo-radiotherapy with a single cycle of Carboplatin (90 mg/mq/die for days 1 to 4) concurrent with radiotherapy (daily radiation dose of 180 cGy for a total dose of 5040 cGy). Two patients have been excluded from the study. When the remaining 71 patients were re-staged, 33 (46%) patients had a major clinical response (>50%), 36 (51%) had minimal response (~50%) or no change and in 2 (3%) patients there was progression of disease. Forty-four patients were judged to be resectable; 2 patients refused surgery and 10 patients could not undergo surgery due to poor respiratory function. Thirty-two patients underwent surgery (25 staged llla and 7 Illb). Thirty of the 32 operated patients were completely resected (resectability rate in patients who underwent surgery after restaging was 94%; overall resectability rate was 41%). Overall pathological downstaging rate was 60% (19/32) with 3 (10%) complete responses and 6 (20%) cases in which only microscopic neoplastic foci were found in the specimen. In the two patients who underwent explorative thoracotomy we confirmed clinical staging (T3N2; T4N2). The overall median two years suwival is 17 months with a follow up range of 2-86 months (median 23 months). There is a statistically significant difference in median survival between patients who underwent surgery - 29 months - and those who didn’t - 14 months (p = 0.0000). The actuarial survival (life table analysis) following complete resection is 45% at five years while it is 8% at 3 years and 0% at 5 years in the group who didn’t have surgery (p = 0.0000). The following conclusions are possible: preoperative radiotherapy and chemotherapy, utilizing Carboplatin, is well tolerated by patients, does not lead to postoperative complications and produces an high rate of response; there is a high resection rate for patients who respond to therapy: good long term survival have been obtained in patients with major response who underwent complete surgical resection.
I351
Combined treatment of inoperable non-small cell lung cancer (NSCLC): Brachv-, teleradio-, chemo-, laskherapy . -
V. Kolek, B. Gronych, K. Cwiertka, G. Engel. Unir Klinikum Ingolsfadt, GER, Czech Republic
of O/omouc,
CR
An optimal algorithm of the combined treatment of inoperable NSCLC doesn’t exist, but there may be some rational preferences. The present study evaluates retrospectively the mean survival (MS) after brachytherapy (BT) and teleradiotherapy (TRT) combined with chemotherapy (ChT) or lasertherapy (LT). Forty one consecutive patients (pts) with local advanced NSCLC were evaluated. The mean age of 37 men and 4 women was 57 years (40-76). Squamous carcinoma was present in 38, adenoca in 2 and giant cell ca in 1 patient. HDR BT (2 x 8 Gy lr-192) and TRT (up to 65 Gy Co-60) were applied to all patients (pts). Nine pts were treated by BT and TRT. ChT using vinorelbin, vepesid, cis- and carboplatin was given to 17 pts (in 8 prior, in 9 after BT and TRT). LT was applied in 28 pts in cases with a central critical obstruction, BT, TRT, ChT and LT was applied to 13 pts. The MS from diaqnosis was 13.5 month (ml in the total series. It was 6.3 m in BT and TR?, 16.8 m in BT, TRT and LT, 20.2 m in BT, TRT and ChT and 12.2 m in BT, TRT, ChT and LT regimen. Those with ChT had MS 14.4 m vs 12.8 m without ChT, those with LT had MS 14.7 m vs 12.2 without LT. All groups treated with radiotherapy combinated with other treatment had a longer survival that pts treated with radiotherapy alone. ChT brought a MS prolongation of 14 m, LT of 10 m, but combination of both therapies (ChT and LT) only 6 m. We conclude that larger and prospective studies on this topic are needed.
Therapy
13521 Induction chemotherapy (ICT cisplatin and vinorelbine) followed by a combination of daily irradiation and carboplatine (CBDCA) in stage IIIB non small cell lung cancer (NSCLC): Final analysis of a phase II trial E. Bardet, J.Y. Douillard, A. Riviere, E. Quoix, D. Spaeth, A. Ducolone, B. Coudert, J.L. Lagrange, P. Chomy, C. Tuchais, B. Pellae-Cosset, M. Henry-Amar. SlvdJ. Rancid, 66805 Nantes, France A phase II trial of induction CT followed by daily CBDCA and radiation was performed in order to evaluate toxicity and efficacy of such a combined modality approach. From 8/94 to l/96, 111 pts were enrolled from 8 centers. Patients population was: male 89, female 12, mean age 58, median PS = 1, 62% squamous cell. No restriction were imposed based on weight lost, supraclavicular lymph node or vena cava syndrome. ICT consisted in Cisplatin (CDDP) 120 mgIma, week 1, 5 and 9 Vinorelbine (NVB) 30 mg/ms week 1 to 9, except week 3 and 7 where dose was reduced to 15 mg/ms. Patients free of distant progression to ICT received megavoltage radiation (66 Gy, 2 Gy/fraction) preceded by 15 mg/m’ CBDCA 2 to 4 hr before radiation daily. Final evaluation was performed 3 months after the end of radiation. As of 12/01/96, 101 patients have been analysed. Received doses of NVB and CDDP were 97 and 78% of scheduled respectively. Grade 3-4 hematological toxicity occurred in 76% of patients. Five patients died before the end of ICT. Response rate was 58% (4 CR, 52 PR), 30 patients were stable, 10 failed including 3 distant progression. Six patients were rendered resectable. Combined CBDCA-radiation was delivered to 75 patients. Delivered dose of CBDCA was 94%, mean dose of radiation 66 Gy. Additional CT identical to induction was given for 2 cycles only to 28 patients, mainly due to toxicity. Response rate to the overall schedule was 52% of evaluable cases, and 35% in intent to treat. Local control at 3 months was achived in 64% evaluable patients and 47% in intent to treat. The 1 year survival rate was 44%. Overall 33 patients died from local progression, 20 from distant metastasis, 4 from treatment related complications, 8 from intercurent disease. Combined ICT followed by concomitant CBDCA-radiation appears feasible in stage IIIB NSCLC, even in an unselected patient population. Contribution of CBDCA as radiosensitizer to improve local control is presently investigated in a phase Ill trial.
I353
Combined chemoradiation therapy for locally advanced resectable non small cell lung cancer (NSCLC)
J.Y. Douillard, E. Bardet, A. Le Groumellec, B. Maury, J. Bennouna, F. Morel, P. Despins. Centre Ren6 Gauducheau 44805 Nanfes-St Herblain, France Neoadjuvant chemotherapy for stage IIIA has proven efficacious in term of survival in randomised trials. In order to possibly improve overall results other modalities have to be evaluated. From May 1995 to April 1996, 9 patients (9 male, mean age 52 y, median PS = 1, squamous cell 8, large cell 1 stage IIIA: 8, 4T2N2, 2T3N2, lT3N1, 1118: 1 T2N3) received concomitant chemoradiotherapy with Vinorelbine 25 ms/m2, lfosfamide 3 mg/m’, Cisplatin 65 mg/m* day 1 and 21 along with 40-45 Gy megavoltage radiation over 4 weeks (2 Gy/fraction, 5 fractions/week). Radical surgery was performed 4 weeks after the end of radiation. Treatment as scheduled was delivered in 8/9 patients, 1 got only one course of chemotherapy for hematotoxicity. Response rate to induction treatment was 1 CR, 5 PR, 3 STB, 0 PRO. All patients were operated on with 8/9 totally resected. One, initially IIIB had an incomplete resection. One patient was tumor free at histology, 5 showed minimal microscopic residual tumor, 3 presented with macroscopic residual disease. One patient died from sepsis within 27 days after surgery. With a median follow-up of 10 months, 6/9 are in complete remission, 1 patient died of distant progression at 6 months, one died from respiratory distress due to Bronchiolitis obliterans. Based on this limited series, combined chemoradiation seem feasable in patients with resectable locally advanced NSCLC and should be investigated in phase Ill as compared to the use of chemotherapy alone.