- Email: [email protected]
The survival of patients treated for limited stage small cell lung cancer has increased during the past 20 years
Combined Modality Therapy~Small
96
Results: S-results per arm: A: operated 41/44 (exploratory S 6•44, R1/R2 9/44, R0 26•44). B: one pt still on treatment (CTx/RTx); operated 29•45 (exploratory S 0/45, RI/R2 7/45, R0 22•45). Treatment related deaths: A: 1/44 pts (infection 1); B: 3/45 pts (sepsis 1, tumor bleeding 1, postoperative bleeding 1). Major 4 ° toxicities in arm B: leucopenia 5 pts, thrombocytopenia 4 pts, anemia 1 pt, infection 1 pt, esophagitis 1 pts, polyneuropathy 1 pt. Median (med) follow-up of all pts still alive (12/99) is 18 months (mo) (1+-60+). Med survival: all 89 pts 21 mo (3Y-SR 36%); all 48 R0-pts 44 mo (3¥-SR 53%). Conclusions: First toxicity analyses indicate, that our trimodality protocol proves safe and feasible in the multicanter phase-Ill setting. Treatment related toxicities in the trimodality arm seem to be reduced compared with those reported from the phasell. Pt accrual continues for this small and selected pt population of operable Ilia (minimal N2). Planned interim analysis of survival per arm will he performed at 110 pts Sponsored by "Deutsche Krebshilfe".
Thursday, 14 September 2000
8:30-10:00
Both disappointing long term survival and limitations of introducing early (concurrent) irradiation have lead us to adopt newer and more promising chemotherapeutic combinations. The protocol of Hainsworth (JCO 15; 1997) was modified and tested in several centers in the Netherlands. Patients with confirmed SCLC LD were treated with Carboplatin (AUC 6), Taxol 200 mg.m-2, Etoposide (2 × 50 mg orally for 5 days) q3 (CTE) for 4 cycles. Concurrent conformal radiotherapy was given to the primary tumor and involved lymph nodes (25 x 1.8 Gy) during the 2nd and 3td cycle. PCI was given at the end of treatment (12 x 2.5 Gy). Since January '99, 15 patients were entered (10 M/5 F, mean age 56 yrs, PS WHO < 2). Ten patients are evaluable for response and 15 for acute toxicity. A total of 57 courses were administered. Toxicity (grade 3 & 4) according to CTC criteria consisted of teukocytopenia 7 pts, thrombocytopenia 3 pts, febrile neutropenia 3 pts, esophagitis 3 pts (one patient could not complete the RT schedule), nausea 2 pts, fatigue 2 pts. Responses (10 evaluable pts): 6 CR, 4 PR. Conclusions: These early data indicate that CTE given with concurrent conformal radiotherapy seems feasible. Hematological toxicity and esophagitis are frequently observed. We therefore continue this study.
ORAL SESSION
Combined
Modality Therapy/Small
r - 3 ~ The survival of patients treated for limited stage small cell lung cancer has increased during the past 20 years P.A. Janne, B. Freidlin, S. Saxman, B.E. Johnson. Dana Farber Cancer Institute, Boston, MA; Biometric Research Branch, NCI, Bethesda, MD; Cancer Therapy Evaluation Program, NCI, Bethesda, MD; Dana Farber Cancer Institute, Boston, MA, USA The survival of patients with both stages of small cell lung cancer (SCLC) and patients with extensive stage SCLC has increased over the past 20 years. In order to determine the trends in survival for patients with limited stage SCLC, we examined data from clinical trials performed by co-operative groups in North America. We reviewed the 20 phase III clinical trials of patients with limited stage SCLC performed in the United States between 1972 and 1996. In addition, patients treated for limited stage SCLC listed in the Surveillance, Epidemiology, and End Results (SEER) database during the same time period were also examined. The median of median survivals in the control arms in phase III studies initiated between 1972 and 1981 was 11.8 months and increased to 16.8 months between 1982 and 1990. Analysis of data from the SEER database demonstrates that between 1973 to 1987 the median survival of patients with limited stage SCLC was 10.6 months and increased to 15.1 months between 1988-1996 (p < 0.0001 for trend in median survival). Since the mid-1970s to the early 9Os, the'five year survival of patients with limited stage small cell lung cancer listed in the SEER database has more than doubled from 5.2% to 12.2% (p = 0.0001 for trend in 5-year survival). The number of patients treated on clinical trials has also increased from a median (in the control arms) of 57 (1972-1981) to 151 (1982-1990) during this time period. Analysis of these 20 studies shows that there has been significant improvement in the median and five year survival of patients with limited stage SCLC over the past 20 years. Given the increase in survival of all patients with SCLC, these findings are unlikely to be caused by stage migration because of more sensitive staging modalities.
•
Concurrent radiation therapy in Small Cell Lung Cancer (SCLC) LD; Preliminary results from a Dutch pilot study J. Belderbos, J. van Meerbeeck, C. Weenink. NKI/AVL, Amsterdam; University Hospital Rotterdam, Rotterdam, The Netherlands In many European countries the standard therapy for SCLC LD is based on non platinum combinations and sequential radiotherapy.
l-3-~ Small cell lung cancer (SCLC): Optimization of treatment by addition of prophylactic cranial irradiation (PCI) and interferon alfa (IFN) B. Lebeau, P. de La Salmoniere, G. Ozenne, F. Blanchon, I? Leclerc, D. Coetmeur, L. Thiberville, T. Urban, A. Legeais. "Petites Cellules"
Group; Dept of Lung Diseases, St Antoine Hospital, AP-HP, Paris, France IFN alfa has already proved efficacy in a wide lot of neoplastic diseases. For SCLC, its benefits on survival is still controversial. We conduced a randomized clinical trial, including 152 pts with SCLC in complete response after 6 cures of chemotherapy. Pts were randomized at the end of this treatment to receive either 3 million IU of IFN alfa 2b, SC, 3 times a week over one year or no IFN until relapse. There was a trend towards extended survival in IFN arm compared with control (p = 0.20) with estimated 2-year survival rates of 23.5% and 14.6% respectively, rates comparable to those of positive previous studies (ASCO, 1999). In this complementary work, we want to study role of PCI for optimizing results, knowing that in the prewritten protocol PCI was optionnal but advised and that curative irradiation was always done for initial cerebral metastases reducing number of pts for this study to 142. Advices are difficult to follow for new practices 41 pts received PCI and 101 didn't. Results are as following table:
Pts nb (Lim/ext)
PCI + IFN IFN alone PCI alone No add ttmt
24 55 17 46
(21/3) (29126) (11/6) (28/18)
Median survival (months) 21.6 9.5 8.7 10.25
Survival rates (%) Deaths rib after randomization
16 50 16 40
1 year
2 year
66.7 40.0 35.3 39.1
40.4 18.2 14.7 15.2
Addition of PCI and IFN has a statistically significative advantage (log-rank test; p = 0.025). This result is to interpret cautiously because this study was not predefined in the trial. There is an imbalance in repartition of limited forms favouring IFN-PCI association but study of limited forms alone let a 2 year survival of 41.3% vs 21.4% in favour of PCI + IFN. (p = 0.17). For pts with SCLC in complete response, curability seems increased by use of treatments acting by different means on residual microscopic disease.
96
Results: S-results per arm: A: operated 41/44 (exploratory S 6•44, R1/R2 9/44, R0 26•44). B: one pt still on treatment (CTx/RTx); operated 29•45 (exploratory S 0/45, RI/R2 7/45, R0 22•45). Treatment related deaths: A: 1/44 pts (infection 1); B: 3/45 pts (sepsis 1, tumor bleeding 1, postoperative bleeding 1). Major 4 ° toxicities in arm B: leucopenia 5 pts, thrombocytopenia 4 pts, anemia 1 pt, infection 1 pt, esophagitis 1 pts, polyneuropathy 1 pt. Median (med) follow-up of all pts still alive (12/99) is 18 months (mo) (1+-60+). Med survival: all 89 pts 21 mo (3Y-SR 36%); all 48 R0-pts 44 mo (3¥-SR 53%). Conclusions: First toxicity analyses indicate, that our trimodality protocol proves safe and feasible in the multicanter phase-Ill setting. Treatment related toxicities in the trimodality arm seem to be reduced compared with those reported from the phasell. Pt accrual continues for this small and selected pt population of operable Ilia (minimal N2). Planned interim analysis of survival per arm will he performed at 110 pts Sponsored by "Deutsche Krebshilfe".
Thursday, 14 September 2000
8:30-10:00
Both disappointing long term survival and limitations of introducing early (concurrent) irradiation have lead us to adopt newer and more promising chemotherapeutic combinations. The protocol of Hainsworth (JCO 15; 1997) was modified and tested in several centers in the Netherlands. Patients with confirmed SCLC LD were treated with Carboplatin (AUC 6), Taxol 200 mg.m-2, Etoposide (2 × 50 mg orally for 5 days) q3 (CTE) for 4 cycles. Concurrent conformal radiotherapy was given to the primary tumor and involved lymph nodes (25 x 1.8 Gy) during the 2nd and 3td cycle. PCI was given at the end of treatment (12 x 2.5 Gy). Since January '99, 15 patients were entered (10 M/5 F, mean age 56 yrs, PS WHO < 2). Ten patients are evaluable for response and 15 for acute toxicity. A total of 57 courses were administered. Toxicity (grade 3 & 4) according to CTC criteria consisted of teukocytopenia 7 pts, thrombocytopenia 3 pts, febrile neutropenia 3 pts, esophagitis 3 pts (one patient could not complete the RT schedule), nausea 2 pts, fatigue 2 pts. Responses (10 evaluable pts): 6 CR, 4 PR. Conclusions: These early data indicate that CTE given with concurrent conformal radiotherapy seems feasible. Hematological toxicity and esophagitis are frequently observed. We therefore continue this study.
ORAL SESSION
Combined
Modality Therapy/Small
r - 3 ~ The survival of patients treated for limited stage small cell lung cancer has increased during the past 20 years P.A. Janne, B. Freidlin, S. Saxman, B.E. Johnson. Dana Farber Cancer Institute, Boston, MA; Biometric Research Branch, NCI, Bethesda, MD; Cancer Therapy Evaluation Program, NCI, Bethesda, MD; Dana Farber Cancer Institute, Boston, MA, USA The survival of patients with both stages of small cell lung cancer (SCLC) and patients with extensive stage SCLC has increased over the past 20 years. In order to determine the trends in survival for patients with limited stage SCLC, we examined data from clinical trials performed by co-operative groups in North America. We reviewed the 20 phase III clinical trials of patients with limited stage SCLC performed in the United States between 1972 and 1996. In addition, patients treated for limited stage SCLC listed in the Surveillance, Epidemiology, and End Results (SEER) database during the same time period were also examined. The median of median survivals in the control arms in phase III studies initiated between 1972 and 1981 was 11.8 months and increased to 16.8 months between 1982 and 1990. Analysis of data from the SEER database demonstrates that between 1973 to 1987 the median survival of patients with limited stage SCLC was 10.6 months and increased to 15.1 months between 1988-1996 (p < 0.0001 for trend in median survival). Since the mid-1970s to the early 9Os, the'five year survival of patients with limited stage small cell lung cancer listed in the SEER database has more than doubled from 5.2% to 12.2% (p = 0.0001 for trend in 5-year survival). The number of patients treated on clinical trials has also increased from a median (in the control arms) of 57 (1972-1981) to 151 (1982-1990) during this time period. Analysis of these 20 studies shows that there has been significant improvement in the median and five year survival of patients with limited stage SCLC over the past 20 years. Given the increase in survival of all patients with SCLC, these findings are unlikely to be caused by stage migration because of more sensitive staging modalities.
•
Concurrent radiation therapy in Small Cell Lung Cancer (SCLC) LD; Preliminary results from a Dutch pilot study J. Belderbos, J. van Meerbeeck, C. Weenink. NKI/AVL, Amsterdam; University Hospital Rotterdam, Rotterdam, The Netherlands In many European countries the standard therapy for SCLC LD is based on non platinum combinations and sequential radiotherapy.
l-3-~ Small cell lung cancer (SCLC): Optimization of treatment by addition of prophylactic cranial irradiation (PCI) and interferon alfa (IFN) B. Lebeau, P. de La Salmoniere, G. Ozenne, F. Blanchon, I? Leclerc, D. Coetmeur, L. Thiberville, T. Urban, A. Legeais. "Petites Cellules"
Group; Dept of Lung Diseases, St Antoine Hospital, AP-HP, Paris, France IFN alfa has already proved efficacy in a wide lot of neoplastic diseases. For SCLC, its benefits on survival is still controversial. We conduced a randomized clinical trial, including 152 pts with SCLC in complete response after 6 cures of chemotherapy. Pts were randomized at the end of this treatment to receive either 3 million IU of IFN alfa 2b, SC, 3 times a week over one year or no IFN until relapse. There was a trend towards extended survival in IFN arm compared with control (p = 0.20) with estimated 2-year survival rates of 23.5% and 14.6% respectively, rates comparable to those of positive previous studies (ASCO, 1999). In this complementary work, we want to study role of PCI for optimizing results, knowing that in the prewritten protocol PCI was optionnal but advised and that curative irradiation was always done for initial cerebral metastases reducing number of pts for this study to 142. Advices are difficult to follow for new practices 41 pts received PCI and 101 didn't. Results are as following table:
Pts nb (Lim/ext)
PCI + IFN IFN alone PCI alone No add ttmt
24 55 17 46
(21/3) (29126) (11/6) (28/18)
Median survival (months) 21.6 9.5 8.7 10.25
Survival rates (%) Deaths rib after randomization
16 50 16 40
1 year
2 year
66.7 40.0 35.3 39.1
40.4 18.2 14.7 15.2
Addition of PCI and IFN has a statistically significative advantage (log-rank test; p = 0.025). This result is to interpret cautiously because this study was not predefined in the trial. There is an imbalance in repartition of limited forms favouring IFN-PCI association but study of limited forms alone let a 2 year survival of 41.3% vs 21.4% in favour of PCI + IFN. (p = 0.17). For pts with SCLC in complete response, curability seems increased by use of treatments acting by different means on residual microscopic disease.