- Email: [email protected]
Induction treatment in patients with lung cancer
Combined Modafity Therapy/Neo non-Small Median progression-free survival: 14 mos, median survival: 20 mos (CI 18-26), 1 yr: 73% (CI 62-84), 2 yr: 47% (CI 32-61). Conclusions: Consolidation docetaxel following concurrent PE/RT is feasible and tolerable. Neutropenia is dose-limiting. Survival in SWOG 9504 in pathologically documented Stage IIIb NSCLC is highly encouraging. Further study of this regimen is warranted.
I-~--~ Phase Ill comparison of sequential vs concurrent chemoradiation for pts with unresected stage III non-small cell lung cancer (NSCLC): Report of Radiation Therapy Oncology Group (RTOG) 9410 W. Curran, C. Scott, C. Langer, R. Komaki, J. Lee, S. Hauser, B. Movsas, T. Wasserman, A. Russell, R. Byhardt, W. Sause, J. Cox.
RTOG, Phila., PA 19107, USA From 7/94-7/98, 611 patients with newly diagnosed, unresected stage I1-111 NSCLC, KPS _> 70, & wt loss < 5% were enrolled in a phase III trial comparing two concurrent chemotherapy (CHM) and thoracic radiotherapy (TRT) regimens to a standard sequential CHM and TRT approach. The sequential arm (SEQ) included cisplatin (P) 100 mg/m-2 days (D) 1 and 29 & vinblastine 5 mg/m-2/weekly × 5 with 60 Gy TRT beginning D 50, and arm 2 used the same CHM with 60 Gy TRT beginning D 1 (CON-QD). Arm 3 employed P 50 rag/m-2 D 1, 8, 29, & 36 with oral VP-16 50 mg BID × 10 weeks 1, 2, 5, & 6 with 69.6 Gy in 1.2 Gy BID fractions beginning D 1 (CON-BID). Of the 597 analyzable pts, the rates of grade 3-4 non-hematologic (N-H) toxicity rates were higher with concurrent than sequential therapy, but late toxicity rates were similar. No difference in grade 5 toxicity rates is noted. With minimum and median potential follow-up times of 15 and 40 months respectively, results are as follows:
93
radiation during first 2 wks of each cycle with chemo repeated on day 29. 163 pts were eligible for analysis. 81 pts were treated on Arm 1 and 82 on Arm 2. Pretreatment characteristics were similar, 64% had stage IIIB in Arm 1 and 66% in Arm 2. There was significantly higher acute esophagitis in Arm 2 compared to Arm 1 (6%) (p = <0.0001). Late chronic esophageal toxicity was significantly more in Arm 2 (17%) compared to Arm 1 (4%) (p = 0.003). Complete response rates were 37% in Arm 1 and 42% in Arm 2 and partial response rate was 36% in Arm 1 and 29% in Arm 2. There was a significant difference in time-to-infield progression (p = 0.009) favoring Arm 2, where 26% vs 45% failed in 2 yrs and 30% vs 49% failed compared to 45% in 2 yrs and 49% in 4 yrs in Arm 2 and Arm 1, respectively. Time to metastasis, overall survival and progression-free survival were similar. Median overall survival was 16.4 mos in Arm 1 and 15.5 mos in Arm 2 (p = 0.88). 2-yr overall survival was 39% in Arm 1 and 32% in Arm 2.5-yr survival was 13% in Arm 1 and 16% in Arm 2. Concurrent chemo and hyperfractionation showed significant improvement of timeto-infield progression with higher acute and chronic esophagitis. Better systemic treatment and chemo-radio protection with conformal RT and concurrent chemotherapy will be investigated.
Wednesday, 13 September 2000
10:30-12:00
ORAL SESSION
Combined Modality TherapylNeo non-Small ~-~
ARM
GR 3-5 ACUTE/LATE N-H TOX
MST
SEQ CON-QD CON-BID
30%/14% 48%/15% 62%/16%
14.6 Mo 17.0 Mo 15.6 Mo
P VALUE VS SEQ
0.08 0.55
These preliminary survival results for the concurrent platinum-based CHM and daily TRT arm (CON-QD) are quite promising and strongly support the continued investigation of concurrent CHM-TRT strategies for patients with locally advanced NSCLC.
•4]
Randomized chemoradiation for patients with locally advanced inoperable non-small cell lung cancer (NSCLC): Long-term follow-up of RTOG 92-04
R. Komaki, W. Seiferheld, D. Ettinger, J.S. Lee, B. Movsas, W. Sause.
UT M.D. Anderson Cancer Center, Houston, TX; RTOG Headquarters, Philadelphia, PA; The Johns Hopkins Oncology Center, Baltimore, MD; Fox Chase Cancer Center Philadelphia, PA; LDS Hospital Salt Lake City, UT, USA Combined chemoradiation is standard treatment for locally advanced inoperable NSCLC and good prognostic factors. Sequencingfractionation of 2 modalities is controversial. In RTOG 92-04, 168 pts with stage II or III disease, KPS > 70, >18 yrs, minimal wt loss < 5%, and adequate renal function and blood count were entered prospectively from 1992-1994. Arm 1 consisted of vinblastine, 5 mg/m2 IV bolus weekly, first 5 wks and cisplatin, 100 mg/m2 IV days 1 and 29 as induction chemotherapy followed by concurrent cisplatin, 75 mg/m2 IV days 50, 71 and 92 during thoracic radiation of 63 Gy in 34 Fx over 7 wks started on day 50. Arm 2 was concurrent chemoradiation started on day 1. A 1.2 Gy/Fx twice daily fractionation was given, at least 6 hrs interfractional invertal 5 days/wk. Total dose was 69.6 Gy in 58 Fx over 6 wks. Chemotherapy was cisplatin, 50 mg/m2 IV days 1 and 8 and oral VP-16, 100 mg/day, 50 mg Bid for 10 days only on days of
Limited toxicity in IIIAJB lung cancer patients treated with neoadjuvant concomitant chemo-twice daily radiation and G-CSF support S. Malamud, B. Culliney, J. Pisch, H. Yu, S. Keller. Beth Israel Medical Center, New York, New York, USA
Sixty-nine patients with Stage Ill A/B Non-Small Cell Lung Cancer were treated with concomitant neoadjuvant chemoradiation therapy from October 1994 to March 1999. Radiation therapy was administered twice daily as 1.5 Gy dose fractions. A six hour gap separated the 2 fractions. Total dose was 45 Gy for patients undergoing surgery, and 60 Gy for patients felt unresectable. During the first and fourth week of treatment patients received either paclitaxel (30 mg/m2/d) D1-4 and cisplatin (100 mg/m 2) on D5 or etoposide (80 mg/m2/d) D1-3 and cisplatin (100 mg/m 2) on D4. G-GSF (filgrastim) 300 mcg was begun on Day 8 and continued for 10 days during cycle one and 5 days during cycle 2. This program was well tolerated; acute toxicity included myelosuppression, esophagitis, dehydration, electrolyte changes and increased salivation. Eight patients required hospital admission (11.6%), five (7%) for hydration, one for neutropenic fever, and two (3%) for sepsis. All patients recovered and went on to complete treatment. There were 11 treatment interruptions (17.4%) due to acute toxicity Early and late toxicity data, local control results and survival data are mature and will be presented.
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3
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Induction treatment in patients with lung cancer
M. Pe,~ek1, K. Nov~k 2, G. (~ertikova 1, A. Tauchman I , B. Eliasov;~ 1.
1Dept. of Tuberculosis and Pulmonary Diseases, Faculty of Medicine, Plzef~, 2Dept. of Surgery, Faculty of Medicine, Plzet~, Czech Republic The authors describe the results of the reduction chemotherapy rarely combined with radiotherapy in patients treated for lung cancer from 1986 year. A group of 60 patients (49 men, 11 women, average age: 56.1, median age: 55.5) with lung cancer (34 pts epidermoid ca, 10 pts adenocarcinoma, 9 pts anaplastic large cell, and 7 pts oat cell carcinoma/SCLC/) presented at the start of the treatment with the following stages: st. I - 6 pts, st. II - 2 pts, st. IIIA/IIIB - 49 pts, st. IV - 3 pts.
94
Combined Modality Therapy/Neo non-Small
The most frequently used induction chemotherapy regimens were: (gemcitabine-cisplatin IGPI in 14 pts, vinorelbine-ifosfamide-cisplatin NIPI in 12 pts, vinblastin-cisplatin (8 pts), taxol-carboplatin fTC/in 8 pts, VP 16-doxo-cisplatin in 5 pts). Moreover, 4 pts received concomitant and 3 sequential chemoradiotherapy. After the induction treatment the surgery was done: in 30 pts - Iobectomy, in 13 pts - bilobectomy, and in 15 pts pneumonectomy, in 1 exploratory thoracotomy, and in 1 incomplete resection of the tumor. Early postoperative mortality was 3 pts (5%), median survival after the radical surgery was 23 months, survival at 2 resp. 3 years was 48.8% resp. 24.4%. MST for the stage III was 24 months. The median survival for different histology types was: epidermoid Ca 24 months, SCLC 22.5 months, adenoca 14 months, anapiastic 11.5 months. Patients treated by the GP combination have MST 18 months, ORR 45%, and after the VIP regimen median followup time/MFT/14 months, ORR 55%, till now 10 out of 11 are alive. The results after the TC regimen were: MFT 12 months (range 9-27), ORR 61%, the MST was not reached. The TC combination was effective also as a neoadjuvant 2nd line therapy. The proportion of surviving patients treated by Iobectomy, bilobectomy or pneumonectomy is not changed during the long term follow-up, so it seems that the extent of surgery itself is not the factor influencing the patient's survival.
[-~
Neoadjuvant radiotherapy treatment for Stage N2 disease NSCLC V.A. Porhanov, I.S. Poliakov, S.S. Semendiaev, V.B. Kononenko, A.N. Bocharov, V.N. Bodnia, M.U. Mamelov. Thoracic Surgery Department, Krasnodar, Russia Objective: Frequent postoperative complications resulted from preoperative radiotherapy make neoadjuvant induction therapy doubtful. Materials and Methods: Since 1992 to 1998 we observed 106 patients that had been administered a full course of preoperative and postoperative radiotherapy in different modes. All of them had Stage N2 disease of NSCLC. Staging was performed previously to treatment by means of fibrinoscopy, CT and mediastinoscopy. Mode 1 included preoperative irradiation of 40 Gy with 2-2.5 Gy-daily standard fractination with further surgery in 3 weeks (72 patients). Mode 2 administered a single fraction of 7.5 Gy with surgery on next day in 34 patients. Preoperatively patients underwent second course of radiotherapy in 3-4 week. There were 90 patients in the control group which underwent surgery alone. Results: Comparing to the control group we observed higher level of blood loss and purulent septic complications, hospital mortality in patients with mode 1 treatment. Complication range had no difference from that in control group. 5-year survival was 21% in the 1 group, 29% in the 2 and 23% in the control group. Conclusions: Introduction of 'short' neoadjuvant mode does not increase hospital mortality and we have observed increased 5-year survival.
[•
Correlation of morphometric tumor response after induction chemotherapy with Docetaxel (D) or Paclitaxel (P) and Carboplatin (C) in stage III NSCLC
F. Griesinger 1, J. Paul1, C.P. Criee 2, H. Schmidberger 1, H. Dalichau 1, B. Herse3, B. Hemmerlein 1. 1University of GSttingen, GOttingen;
2Lung Hospital of Lenglern, Bovenden; 3Central Clinic of Erfurt, Erfurt, Germany Objective: D/C combination chemotherapy has shown high response rates in advanced NSCLC. The aim of this phase II study was to correlate morphometric response after 4 cycles of D 100 mg/m2 or P 200 mg/m2 dl, C AUC 7, 5 d2 q3 weeks with disease free survival in NSCLC IIIB patients. Patients and Methods: 31 patients with histologically proven stage IliB NSCLC were enrolled to receive Docetaxel and Carboplatin for 4 cycles. Responding patients were evaluated for surgery after 4 cycles, postoperative mediastinal radiotherapy was administered. Morphometry was carried out according to the criteria established by Junker et al., 1993.
Results: On an intent to treat basis, the radiologic ORR was 71%, the R0 resection rate was 52%. Kaplan Meier analysis of survival indicates a plateau at 24% with a median follow-up of survivors of 25 months (17-44 months). Regression grades III and liB were found in 9/20 (45%) resected patients (all R0) with a survival estimate at 89% (median follow-up 25 months, 17-44 months). Regression grades I and IIA were observed in 11/20 (55%) resected patients (4 Rl/2, 7 R0) with all patients having succumbed to their disease at 30 months. Conclusion: D/P-C combination induction chemotherapy in NSCLC IIIB is effective, morphometric response of mediastinal lymph nodes and primary tumor is highly associated with long term survival and systemic tumor control.
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Positron emission tomography (PET) assessment of response to neoadjuvant chemotherapy in stage II and Ilia non-small cell lung cancer
M. Harris, R. De Boer, S. Ramdave, S. Berlangieri, S. Knight, C.P. Clarke, F. Daniel, J. Cebon, A.M. Scott, P.L. Mitchell. Austin and
Repatriation Medical Centre, Melbourne, Australia There is increasing evidence for the use of neoadjuvant chemotherapy prior to surgical resection in the treatment of patients (pts) with non-small cell lung cancer (NSCLC). Response to chemotherapy is currently evaluated by CT scanning and it is clear that CT may not be predictive of histological or pt outcome in some cases. FDG PET scanning allows functional evaluation and may provide more accurate assessment of tumour response to chemotherapy. Between 1997 and 1999 19 patients with marginally resectable stage II or IliA NSCLC underwent neo-adjuvant chemotherapy and serial PET scans. Data are currently available for 12 pts: 10 male; median age 64 yrs (range 52-76); median ECOG PS 1 (0-2); stage II 3 pts, stage IliA 9 pts; histologic subtypes: squamous 5, large cell 2, adenocarcinoma 3, mixed NSCLC 2. Staging investigations included CT chest, upper abdomen and brain, bone scan and FDG PET scan. Mediastinoscopy was performed as required to confirm N2 disease. CT and PET scans were repeated after the first and third cycles of chemotherapy to assess response. Pts received three cycles of preoperative chemotherapy given 3-4 weekly: Cisplatin 100 mg/m2 D1, Cyciophosphamide 500 mg/m2 D1, and Etoposide 100 mg/m2 D1-3. Responders could receive three further cycles of chemotherapy postoperatively. Radiotherapy was administered post-operatively for node positive disease or positive margins. Median followup for the 12 pts was 10 mths (range 3-33 mths). By CT criteria, 6 pts (50%) responded to neo-adjuvant chemotherapy (CR 1 pt and PR 5 pts). PET response of the primary tumour concorded with CT response in 3/6 cases. Seven pts had complete resections, 3 incomplete resections and 2 were unresectable. Seven pts remain alive, six in complete remission (4, 6, 13, 14, 25, 33 mths) and one with progressive disease. Four pts have died of progressive disease and one from post-operative pulmonary embolus. Toxicity of grade 3-4 severity included: thrombocytopenia 2 pts, febrile neutropenia 2 pts, vomiting 1 pt, and sensory peripheral neuropathy 1 pt. Six pts received consolidation radiotherapy. These data confirm previous results of high response and resection rates using this chemotherapy regimen. A full comparison of PET with CT assessment of treatment response for all sites of primary and nodal disease, along with histological and patient outcome, will be presented.
•1-•
Patterns of relapse of clinical N2 non-small-cell lung cancer (NSCLC) treated with preoperative chemotherapy: Should propylactic cranial irradiatlon be reconsidered?
F. Andre, D. Grunenwald, J.P. Pignon, J. Pujol, P.Y. Brichon, L. Brouchet, A. Dujon, V. Weestel, T. Le Chevalier. Department of
Medicine, Institut Gustave Roussy, Villejuif, France The aim of the present study was to analyze patterns of relapse of clinical N2 NSCLC treated with preoperative chemotherapy in order to identify the new therapeutic challenges to be considered for these patients. We previously defined clinical N2 (cN2) NSCLC as patients
I-~--~ Phase Ill comparison of sequential vs concurrent chemoradiation for pts with unresected stage III non-small cell lung cancer (NSCLC): Report of Radiation Therapy Oncology Group (RTOG) 9410 W. Curran, C. Scott, C. Langer, R. Komaki, J. Lee, S. Hauser, B. Movsas, T. Wasserman, A. Russell, R. Byhardt, W. Sause, J. Cox.
RTOG, Phila., PA 19107, USA From 7/94-7/98, 611 patients with newly diagnosed, unresected stage I1-111 NSCLC, KPS _> 70, & wt loss < 5% were enrolled in a phase III trial comparing two concurrent chemotherapy (CHM) and thoracic radiotherapy (TRT) regimens to a standard sequential CHM and TRT approach. The sequential arm (SEQ) included cisplatin (P) 100 mg/m-2 days (D) 1 and 29 & vinblastine 5 mg/m-2/weekly × 5 with 60 Gy TRT beginning D 50, and arm 2 used the same CHM with 60 Gy TRT beginning D 1 (CON-QD). Arm 3 employed P 50 rag/m-2 D 1, 8, 29, & 36 with oral VP-16 50 mg BID × 10 weeks 1, 2, 5, & 6 with 69.6 Gy in 1.2 Gy BID fractions beginning D 1 (CON-BID). Of the 597 analyzable pts, the rates of grade 3-4 non-hematologic (N-H) toxicity rates were higher with concurrent than sequential therapy, but late toxicity rates were similar. No difference in grade 5 toxicity rates is noted. With minimum and median potential follow-up times of 15 and 40 months respectively, results are as follows:
93
radiation during first 2 wks of each cycle with chemo repeated on day 29. 163 pts were eligible for analysis. 81 pts were treated on Arm 1 and 82 on Arm 2. Pretreatment characteristics were similar, 64% had stage IIIB in Arm 1 and 66% in Arm 2. There was significantly higher acute esophagitis in Arm 2 compared to Arm 1 (6%) (p = <0.0001). Late chronic esophageal toxicity was significantly more in Arm 2 (17%) compared to Arm 1 (4%) (p = 0.003). Complete response rates were 37% in Arm 1 and 42% in Arm 2 and partial response rate was 36% in Arm 1 and 29% in Arm 2. There was a significant difference in time-to-infield progression (p = 0.009) favoring Arm 2, where 26% vs 45% failed in 2 yrs and 30% vs 49% failed compared to 45% in 2 yrs and 49% in 4 yrs in Arm 2 and Arm 1, respectively. Time to metastasis, overall survival and progression-free survival were similar. Median overall survival was 16.4 mos in Arm 1 and 15.5 mos in Arm 2 (p = 0.88). 2-yr overall survival was 39% in Arm 1 and 32% in Arm 2.5-yr survival was 13% in Arm 1 and 16% in Arm 2. Concurrent chemo and hyperfractionation showed significant improvement of timeto-infield progression with higher acute and chronic esophagitis. Better systemic treatment and chemo-radio protection with conformal RT and concurrent chemotherapy will be investigated.
Wednesday, 13 September 2000
10:30-12:00
ORAL SESSION
Combined Modality TherapylNeo non-Small ~-~
ARM
GR 3-5 ACUTE/LATE N-H TOX
MST
SEQ CON-QD CON-BID
30%/14% 48%/15% 62%/16%
14.6 Mo 17.0 Mo 15.6 Mo
P VALUE VS SEQ
0.08 0.55
These preliminary survival results for the concurrent platinum-based CHM and daily TRT arm (CON-QD) are quite promising and strongly support the continued investigation of concurrent CHM-TRT strategies for patients with locally advanced NSCLC.
•4]
Randomized chemoradiation for patients with locally advanced inoperable non-small cell lung cancer (NSCLC): Long-term follow-up of RTOG 92-04
R. Komaki, W. Seiferheld, D. Ettinger, J.S. Lee, B. Movsas, W. Sause.
UT M.D. Anderson Cancer Center, Houston, TX; RTOG Headquarters, Philadelphia, PA; The Johns Hopkins Oncology Center, Baltimore, MD; Fox Chase Cancer Center Philadelphia, PA; LDS Hospital Salt Lake City, UT, USA Combined chemoradiation is standard treatment for locally advanced inoperable NSCLC and good prognostic factors. Sequencingfractionation of 2 modalities is controversial. In RTOG 92-04, 168 pts with stage II or III disease, KPS > 70, >18 yrs, minimal wt loss < 5%, and adequate renal function and blood count were entered prospectively from 1992-1994. Arm 1 consisted of vinblastine, 5 mg/m2 IV bolus weekly, first 5 wks and cisplatin, 100 mg/m2 IV days 1 and 29 as induction chemotherapy followed by concurrent cisplatin, 75 mg/m2 IV days 50, 71 and 92 during thoracic radiation of 63 Gy in 34 Fx over 7 wks started on day 50. Arm 2 was concurrent chemoradiation started on day 1. A 1.2 Gy/Fx twice daily fractionation was given, at least 6 hrs interfractional invertal 5 days/wk. Total dose was 69.6 Gy in 58 Fx over 6 wks. Chemotherapy was cisplatin, 50 mg/m2 IV days 1 and 8 and oral VP-16, 100 mg/day, 50 mg Bid for 10 days only on days of
Limited toxicity in IIIAJB lung cancer patients treated with neoadjuvant concomitant chemo-twice daily radiation and G-CSF support S. Malamud, B. Culliney, J. Pisch, H. Yu, S. Keller. Beth Israel Medical Center, New York, New York, USA
Sixty-nine patients with Stage Ill A/B Non-Small Cell Lung Cancer were treated with concomitant neoadjuvant chemoradiation therapy from October 1994 to March 1999. Radiation therapy was administered twice daily as 1.5 Gy dose fractions. A six hour gap separated the 2 fractions. Total dose was 45 Gy for patients undergoing surgery, and 60 Gy for patients felt unresectable. During the first and fourth week of treatment patients received either paclitaxel (30 mg/m2/d) D1-4 and cisplatin (100 mg/m 2) on D5 or etoposide (80 mg/m2/d) D1-3 and cisplatin (100 mg/m 2) on D4. G-GSF (filgrastim) 300 mcg was begun on Day 8 and continued for 10 days during cycle one and 5 days during cycle 2. This program was well tolerated; acute toxicity included myelosuppression, esophagitis, dehydration, electrolyte changes and increased salivation. Eight patients required hospital admission (11.6%), five (7%) for hydration, one for neutropenic fever, and two (3%) for sepsis. All patients recovered and went on to complete treatment. There were 11 treatment interruptions (17.4%) due to acute toxicity Early and late toxicity data, local control results and survival data are mature and will be presented.
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0
•
Induction treatment in patients with lung cancer
M. Pe,~ek1, K. Nov~k 2, G. (~ertikova 1, A. Tauchman I , B. Eliasov;~ 1.
1Dept. of Tuberculosis and Pulmonary Diseases, Faculty of Medicine, Plzef~, 2Dept. of Surgery, Faculty of Medicine, Plzet~, Czech Republic The authors describe the results of the reduction chemotherapy rarely combined with radiotherapy in patients treated for lung cancer from 1986 year. A group of 60 patients (49 men, 11 women, average age: 56.1, median age: 55.5) with lung cancer (34 pts epidermoid ca, 10 pts adenocarcinoma, 9 pts anaplastic large cell, and 7 pts oat cell carcinoma/SCLC/) presented at the start of the treatment with the following stages: st. I - 6 pts, st. II - 2 pts, st. IIIA/IIIB - 49 pts, st. IV - 3 pts.
94
Combined Modality Therapy/Neo non-Small
The most frequently used induction chemotherapy regimens were: (gemcitabine-cisplatin IGPI in 14 pts, vinorelbine-ifosfamide-cisplatin NIPI in 12 pts, vinblastin-cisplatin (8 pts), taxol-carboplatin fTC/in 8 pts, VP 16-doxo-cisplatin in 5 pts). Moreover, 4 pts received concomitant and 3 sequential chemoradiotherapy. After the induction treatment the surgery was done: in 30 pts - Iobectomy, in 13 pts - bilobectomy, and in 15 pts pneumonectomy, in 1 exploratory thoracotomy, and in 1 incomplete resection of the tumor. Early postoperative mortality was 3 pts (5%), median survival after the radical surgery was 23 months, survival at 2 resp. 3 years was 48.8% resp. 24.4%. MST for the stage III was 24 months. The median survival for different histology types was: epidermoid Ca 24 months, SCLC 22.5 months, adenoca 14 months, anapiastic 11.5 months. Patients treated by the GP combination have MST 18 months, ORR 45%, and after the VIP regimen median followup time/MFT/14 months, ORR 55%, till now 10 out of 11 are alive. The results after the TC regimen were: MFT 12 months (range 9-27), ORR 61%, the MST was not reached. The TC combination was effective also as a neoadjuvant 2nd line therapy. The proportion of surviving patients treated by Iobectomy, bilobectomy or pneumonectomy is not changed during the long term follow-up, so it seems that the extent of surgery itself is not the factor influencing the patient's survival.
[-~
Neoadjuvant radiotherapy treatment for Stage N2 disease NSCLC V.A. Porhanov, I.S. Poliakov, S.S. Semendiaev, V.B. Kononenko, A.N. Bocharov, V.N. Bodnia, M.U. Mamelov. Thoracic Surgery Department, Krasnodar, Russia Objective: Frequent postoperative complications resulted from preoperative radiotherapy make neoadjuvant induction therapy doubtful. Materials and Methods: Since 1992 to 1998 we observed 106 patients that had been administered a full course of preoperative and postoperative radiotherapy in different modes. All of them had Stage N2 disease of NSCLC. Staging was performed previously to treatment by means of fibrinoscopy, CT and mediastinoscopy. Mode 1 included preoperative irradiation of 40 Gy with 2-2.5 Gy-daily standard fractination with further surgery in 3 weeks (72 patients). Mode 2 administered a single fraction of 7.5 Gy with surgery on next day in 34 patients. Preoperatively patients underwent second course of radiotherapy in 3-4 week. There were 90 patients in the control group which underwent surgery alone. Results: Comparing to the control group we observed higher level of blood loss and purulent septic complications, hospital mortality in patients with mode 1 treatment. Complication range had no difference from that in control group. 5-year survival was 21% in the 1 group, 29% in the 2 and 23% in the control group. Conclusions: Introduction of 'short' neoadjuvant mode does not increase hospital mortality and we have observed increased 5-year survival.
[•
Correlation of morphometric tumor response after induction chemotherapy with Docetaxel (D) or Paclitaxel (P) and Carboplatin (C) in stage III NSCLC
F. Griesinger 1, J. Paul1, C.P. Criee 2, H. Schmidberger 1, H. Dalichau 1, B. Herse3, B. Hemmerlein 1. 1University of GSttingen, GOttingen;
2Lung Hospital of Lenglern, Bovenden; 3Central Clinic of Erfurt, Erfurt, Germany Objective: D/C combination chemotherapy has shown high response rates in advanced NSCLC. The aim of this phase II study was to correlate morphometric response after 4 cycles of D 100 mg/m2 or P 200 mg/m2 dl, C AUC 7, 5 d2 q3 weeks with disease free survival in NSCLC IIIB patients. Patients and Methods: 31 patients with histologically proven stage IliB NSCLC were enrolled to receive Docetaxel and Carboplatin for 4 cycles. Responding patients were evaluated for surgery after 4 cycles, postoperative mediastinal radiotherapy was administered. Morphometry was carried out according to the criteria established by Junker et al., 1993.
Results: On an intent to treat basis, the radiologic ORR was 71%, the R0 resection rate was 52%. Kaplan Meier analysis of survival indicates a plateau at 24% with a median follow-up of survivors of 25 months (17-44 months). Regression grades III and liB were found in 9/20 (45%) resected patients (all R0) with a survival estimate at 89% (median follow-up 25 months, 17-44 months). Regression grades I and IIA were observed in 11/20 (55%) resected patients (4 Rl/2, 7 R0) with all patients having succumbed to their disease at 30 months. Conclusion: D/P-C combination induction chemotherapy in NSCLC IIIB is effective, morphometric response of mediastinal lymph nodes and primary tumor is highly associated with long term survival and systemic tumor control.
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Positron emission tomography (PET) assessment of response to neoadjuvant chemotherapy in stage II and Ilia non-small cell lung cancer
M. Harris, R. De Boer, S. Ramdave, S. Berlangieri, S. Knight, C.P. Clarke, F. Daniel, J. Cebon, A.M. Scott, P.L. Mitchell. Austin and
Repatriation Medical Centre, Melbourne, Australia There is increasing evidence for the use of neoadjuvant chemotherapy prior to surgical resection in the treatment of patients (pts) with non-small cell lung cancer (NSCLC). Response to chemotherapy is currently evaluated by CT scanning and it is clear that CT may not be predictive of histological or pt outcome in some cases. FDG PET scanning allows functional evaluation and may provide more accurate assessment of tumour response to chemotherapy. Between 1997 and 1999 19 patients with marginally resectable stage II or IliA NSCLC underwent neo-adjuvant chemotherapy and serial PET scans. Data are currently available for 12 pts: 10 male; median age 64 yrs (range 52-76); median ECOG PS 1 (0-2); stage II 3 pts, stage IliA 9 pts; histologic subtypes: squamous 5, large cell 2, adenocarcinoma 3, mixed NSCLC 2. Staging investigations included CT chest, upper abdomen and brain, bone scan and FDG PET scan. Mediastinoscopy was performed as required to confirm N2 disease. CT and PET scans were repeated after the first and third cycles of chemotherapy to assess response. Pts received three cycles of preoperative chemotherapy given 3-4 weekly: Cisplatin 100 mg/m2 D1, Cyciophosphamide 500 mg/m2 D1, and Etoposide 100 mg/m2 D1-3. Responders could receive three further cycles of chemotherapy postoperatively. Radiotherapy was administered post-operatively for node positive disease or positive margins. Median followup for the 12 pts was 10 mths (range 3-33 mths). By CT criteria, 6 pts (50%) responded to neo-adjuvant chemotherapy (CR 1 pt and PR 5 pts). PET response of the primary tumour concorded with CT response in 3/6 cases. Seven pts had complete resections, 3 incomplete resections and 2 were unresectable. Seven pts remain alive, six in complete remission (4, 6, 13, 14, 25, 33 mths) and one with progressive disease. Four pts have died of progressive disease and one from post-operative pulmonary embolus. Toxicity of grade 3-4 severity included: thrombocytopenia 2 pts, febrile neutropenia 2 pts, vomiting 1 pt, and sensory peripheral neuropathy 1 pt. Six pts received consolidation radiotherapy. These data confirm previous results of high response and resection rates using this chemotherapy regimen. A full comparison of PET with CT assessment of treatment response for all sites of primary and nodal disease, along with histological and patient outcome, will be presented.
•1-•
Patterns of relapse of clinical N2 non-small-cell lung cancer (NSCLC) treated with preoperative chemotherapy: Should propylactic cranial irradiatlon be reconsidered?
F. Andre, D. Grunenwald, J.P. Pignon, J. Pujol, P.Y. Brichon, L. Brouchet, A. Dujon, V. Weestel, T. Le Chevalier. Department of
Medicine, Institut Gustave Roussy, Villejuif, France The aim of the present study was to analyze patterns of relapse of clinical N2 NSCLC treated with preoperative chemotherapy in order to identify the new therapeutic challenges to be considered for these patients. We previously defined clinical N2 (cN2) NSCLC as patients