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886 Poster Induction chemotherapy (CT) followed by concurrent Cisplatin and accelerated radiotherapy in locally advanced non-small cell lung cancer (NSCLC)
$262 Friday/Saturday, 20-21 September 2002
amount of normal lung treated, 884
Poster
Influence of interfraction interval on treatment outcome in p a t i e n t s with locally advanced nonmetastatic non-small cell lung cancer treated with hyperfractionated radiation therapy with or without concurrent chemotherapy. Final results in 536 patients B. Jeremic, B. Mi/icic, A. Dagovic, J. A/eksandrovic, S. Bosnjakovic University Hospital, Oncology, Kragujevac, Yugoslavia Purpose: To investigate influence of interfraction interval (IFI) on treatment outcome in patients with stage III non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy (Hfx RT) with or without concurrent chemotherapy (CHT). Material and Methods: During a six-year period, three prospective randomised phase 111 and one prospective phase II study were performed enrolling a total of 536 patients treated with Hfx RT alone or with concurrent carboplatin/etoposide. Two hundred-eighty five patients were treated with IFI of 4.5-5.0 hr, while 251 patients were treated with IFI of 5.5-6.0 hr. Results: "shorter" (4.5-5.0 hr) IFl were superior to "longer" (5.5-6.0 hr) IFI (MST, 25 vs. 12 months; 5- year survival, 27% vs. 8%; p=0.0000). Shorter IFI also led to better LRFS than longer ones (median time, 25 vs. 15 months; 5-year LRFS rates, 37% vs. 16%; p=0.0000). Univariate and multivariate Cox models were used to investigate independent influence of tFI on both overall survival (OS) and LRFS. After correcting for various pretreatment prognostic factors such as gender, age, KPS, weight loss and stage as welt as for treatment-related factors such as RT dose and administration of concurrent CHT, IFI was shown to be an independent prognosticator of both overall survival and LRFS These results were confirmed when we separated all patients (n = 536) into those treated with Hfx RT only (n = 127) and those treated with concurrent RT/CHT (n = 409), using both OS and LRFS as endpoints. Acute and late high-grade (> 3) RT-related toxicity was not different between the two IFI, but patients treated with shorter IFI had significantly highei" incidence of haematological toxicity (p=0.002). Using regression analysis, correlation of various pretreatment and treatment variables with acute and late high-grade (> 3) toxicity showed that IFI was not significant predictor of any of acute or late high-grade (> 3) toxicity, including all toxicity. Conclusions: this study showed that IFI is an important prognosticator of OS and LFRS in patients with stage III NSCLC treated with Hfx RT with or without concurrent carboplatin/etoposide. IFI led to higher incidence only of haematological toxicity, but was not predictive of any acute or late highgrade (> 3) toxicity. 885
Poster
Phase 1/11study evaluating the addition of concurrent twice weekly paclitaxel and cisplatin to radiation therapy [RT] in patients with stage III non-small cell lung cancer [ N S C L C ] D. Ball 1, G. Richardson 2, J. Smith 3, B. So/omon 4, M. Michae/4, C. O" Kane 4, M. Mac Manus 1, A. Wirth 1, G. Ryan 1, D. Rischin 4 1peter MacCa//um Cancer/nstitufe, Radiation Onco/ogy, Me~bourne, Austra/ia 2Monash Medica/ Centre, Medica/ Onco/ogy, Moorabbin, Australia 3peter MacCa//um Cancer/nstitute, Statistica/ Centre, Me~bourne, Australia 4peter MacCa//um Cancer Institute, Medica/ Onco/ogy, Me~bourne, Ausfra/ia Background: Preclinical studies at one of our institutions using a squamous cell carcinoma xenograft have demonstrated better radiosensitisation with daily paclitaxel rather than a single dose (1). We therefore hypothesized that twice weekly administration of paclitaxel concomitant with RT might be more active than weekly administration, Aims: (a) To establish the maximum tolerated dose (MTD) of twice weekly paclitaxel and weekly cisplatin given concurrently with radical RT in patients with stage III NSCLC; and (b) to assess the activity of this regimen. Patients and methods: Patients (pts) who had given written informed consent and who had histologic diagnosis of NSCLC, stage III disease (no pleural effusion or cervical lymphadenopathy), performance status ECOG 0 or 1; weight loss < 10% and no prior treatment for NSCLC were eligible. All pts were planned for RT to the primary site and involved regional nodes 60 Gy in 30 fractions over six weeks. Concurrent paclitaxel was administered twice weekly, with RT and weekly cisplatin 20 mg/m 2, at a starting dose of 20 mg/m 2and in increments of 5 mg/m 2to successive cohorts of 3-6 pts until 3 pts with dose'limiting toxicities (DLT) were observed at a particular dose level. The previous dose level was then defined as the MTD. All pts were
Posters
planned to be given a further 2 cycles of chemotherapy consisting of paclitaxe1175 mg/m 2 and carboplatin AUC 5 after completion of RT. Results: Between 3/99 and 5/01, a total of 25 pts were enrolled in this study from two institutions. All have been followed at least to 19 Nov 2001 (closeout date). At a dose of paclitaxel 35 mg/m 2, 3 of 4 treated pts had DLTs [1 grade III oesophagitis, pulmonary toxicity and fatigue, 1 grade Ill oesophagitis and infection and 1 grade 4 fever and grade 3 allergic reaction]. The MTD was therefore determined to be 30 mg/m2 and a total of 15 pts were enrolled at this level. The overall response rate was 64% (95% C1:43% 82%) and for the expanded cohort 60% (C1:32% - 84%). The estimated 1year survival for all pts was 71%, and for the expanded cohort also 71%. 3 pts developed pectoral muscle injury in the radiation field, including one biopsy proven necrosis. Conclusions: Paclitaxel can be safely given twice weekly with radical RT (60 Gy) and weekly cisplatin 20 mg/m 2 at a dose of 30 mg/mE Ref: (1) Joschko et al, Rad Oncol Invest 1997; 4: 268. 886
Poster
Induction chemotherapy (CT) followed by concurrent Cisplatin and accelerated radiotherapy in locally advanced nons m a l l cell lung cancer (NSCLC)
R. Arriaqada, S. Kleinman, L. Orlandi, B. Roth 1, C. del Castillo, J. Gutierrez, M. Zuniga, R. Baeza IRAM CBLA-IO0 investigators, GOCCHI Instituto Radiomedicina, Radiation Oncology Department, Santiago, Chile This multicentric phase II trial combined three treatment strategies for locally advanced NSCLC in a total treatment time of 100 days: 1) three courses of induction CT; 2) continuous hyperfractionated accelerated radiotherapy without week-end (CHARTWEL) with 3) concurrent use of daily cisplatin (6 mg/m2).Cycles of CT consisted of cisplatin 100 mg/m 2all, vinorelbi'ne(1 ) 25 mg/m 2 dl, 8, 15 or 22. CHARTWEL delivered a total radiation dose of 54 Gy in 36 fractions and t6 days. The aim of the trial was to evaluate feasibility, considering acceptable a 20% rate of grade Ill-IV esophagitis. The second objective was to measure complete remission (CR) rate after d190. Fifty patients were included, 48 fully evaluated for tumor response or dying before evaluation as of 2002/03/30. Patient characteristics, mean age 60, 3% males, 73% stage IIIB. 75% received the intended treatment. Esophagitis grade Ill-IV was 17% (95%, CI: 7-33). One patient died of toxicity after CT. Tumor response ratese (%) are shown in table (denominator is always 48): Tumour response after CT after CHARTWEL CR 2 31 (CI: 9-46) PR > 50% 52 25 (CI: 4-40) No change 25 12 Progression 12 27 Non assessable 8 4 Objective response rate was 56% (CI: 41-70). Five patients underwent surgery after the protocol, one is a long-term survival (more than 3 years). Mean survival is 21 (CI: 15-27) months. Overall survival rates at 1, 2 and 3 years are 48%, 28 and 19%. This new combined treatment modality is feasible, and may allow a wide range of combinations with potential new cytotoxics and a CHARTWEL radical approach for locally advanced NSCLC. (1) In chile, NavelbeneTM was freely provided by Pierre Fabre Oncologie, France. 887 Poster P h a s e II study of concurrent radiochemotherapy (RCT) with
CPT-11/cisplatin in patients (pts) with advanced non small cell lung cancer (NSCLC) G. Klautke 1, R. Fietkau 1, U. Dietrich 1, A. Bier2, P. Ketteret3, A. Thierbach 3 1Department of Radiotherapy, University of Rostock, Rostock, Germany 2Department of Internal Medicine, University of Rostock, Restock, Getmany 3Department of Internal Medicine, Klinikum Suedstadt of Rostock, Rostock, Germany Purpose: The combination of CPT-11 and cis-platin is highly effective against NSCLC and both show synergistic effects with radiation. To assess the efficacy and tocicity of concurrent RCT with cis-platin and CPT - 11 a phase II study was performed. Methods: From 10/98 to 12/01 36 pts (median age64,5 y; Range 49 - 75y) with inoperable or advanced NSCLC (I/115 pts; Ilia 7 pts; IIIB 19 pts; local recurrences 4pts) were treated with conventional fractionated radiation therapy of the macroscopic tumour regions up to 63Gy and the mediastinum up to 45/50,4 Gy. Chemotherapy consisted of CPT-tl 40 mg/m = day
amount of normal lung treated, 884
Poster
Influence of interfraction interval on treatment outcome in p a t i e n t s with locally advanced nonmetastatic non-small cell lung cancer treated with hyperfractionated radiation therapy with or without concurrent chemotherapy. Final results in 536 patients B. Jeremic, B. Mi/icic, A. Dagovic, J. A/eksandrovic, S. Bosnjakovic University Hospital, Oncology, Kragujevac, Yugoslavia Purpose: To investigate influence of interfraction interval (IFI) on treatment outcome in patients with stage III non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy (Hfx RT) with or without concurrent chemotherapy (CHT). Material and Methods: During a six-year period, three prospective randomised phase 111 and one prospective phase II study were performed enrolling a total of 536 patients treated with Hfx RT alone or with concurrent carboplatin/etoposide. Two hundred-eighty five patients were treated with IFI of 4.5-5.0 hr, while 251 patients were treated with IFI of 5.5-6.0 hr. Results: "shorter" (4.5-5.0 hr) IFl were superior to "longer" (5.5-6.0 hr) IFI (MST, 25 vs. 12 months; 5- year survival, 27% vs. 8%; p=0.0000). Shorter IFI also led to better LRFS than longer ones (median time, 25 vs. 15 months; 5-year LRFS rates, 37% vs. 16%; p=0.0000). Univariate and multivariate Cox models were used to investigate independent influence of tFI on both overall survival (OS) and LRFS. After correcting for various pretreatment prognostic factors such as gender, age, KPS, weight loss and stage as welt as for treatment-related factors such as RT dose and administration of concurrent CHT, IFI was shown to be an independent prognosticator of both overall survival and LRFS These results were confirmed when we separated all patients (n = 536) into those treated with Hfx RT only (n = 127) and those treated with concurrent RT/CHT (n = 409), using both OS and LRFS as endpoints. Acute and late high-grade (> 3) RT-related toxicity was not different between the two IFI, but patients treated with shorter IFI had significantly highei" incidence of haematological toxicity (p=0.002). Using regression analysis, correlation of various pretreatment and treatment variables with acute and late high-grade (> 3) toxicity showed that IFI was not significant predictor of any of acute or late high-grade (> 3) toxicity, including all toxicity. Conclusions: this study showed that IFI is an important prognosticator of OS and LFRS in patients with stage III NSCLC treated with Hfx RT with or without concurrent carboplatin/etoposide. IFI led to higher incidence only of haematological toxicity, but was not predictive of any acute or late highgrade (> 3) toxicity. 885
Poster
Phase 1/11study evaluating the addition of concurrent twice weekly paclitaxel and cisplatin to radiation therapy [RT] in patients with stage III non-small cell lung cancer [ N S C L C ] D. Ball 1, G. Richardson 2, J. Smith 3, B. So/omon 4, M. Michae/4, C. O" Kane 4, M. Mac Manus 1, A. Wirth 1, G. Ryan 1, D. Rischin 4 1peter MacCa//um Cancer/nstitufe, Radiation Onco/ogy, Me~bourne, Austra/ia 2Monash Medica/ Centre, Medica/ Onco/ogy, Moorabbin, Australia 3peter MacCa//um Cancer/nstitute, Statistica/ Centre, Me~bourne, Australia 4peter MacCa//um Cancer Institute, Medica/ Onco/ogy, Me~bourne, Ausfra/ia Background: Preclinical studies at one of our institutions using a squamous cell carcinoma xenograft have demonstrated better radiosensitisation with daily paclitaxel rather than a single dose (1). We therefore hypothesized that twice weekly administration of paclitaxel concomitant with RT might be more active than weekly administration, Aims: (a) To establish the maximum tolerated dose (MTD) of twice weekly paclitaxel and weekly cisplatin given concurrently with radical RT in patients with stage III NSCLC; and (b) to assess the activity of this regimen. Patients and methods: Patients (pts) who had given written informed consent and who had histologic diagnosis of NSCLC, stage III disease (no pleural effusion or cervical lymphadenopathy), performance status ECOG 0 or 1; weight loss < 10% and no prior treatment for NSCLC were eligible. All pts were planned for RT to the primary site and involved regional nodes 60 Gy in 30 fractions over six weeks. Concurrent paclitaxel was administered twice weekly, with RT and weekly cisplatin 20 mg/m 2, at a starting dose of 20 mg/m 2and in increments of 5 mg/m 2to successive cohorts of 3-6 pts until 3 pts with dose'limiting toxicities (DLT) were observed at a particular dose level. The previous dose level was then defined as the MTD. All pts were
Posters
planned to be given a further 2 cycles of chemotherapy consisting of paclitaxe1175 mg/m 2 and carboplatin AUC 5 after completion of RT. Results: Between 3/99 and 5/01, a total of 25 pts were enrolled in this study from two institutions. All have been followed at least to 19 Nov 2001 (closeout date). At a dose of paclitaxel 35 mg/m 2, 3 of 4 treated pts had DLTs [1 grade III oesophagitis, pulmonary toxicity and fatigue, 1 grade Ill oesophagitis and infection and 1 grade 4 fever and grade 3 allergic reaction]. The MTD was therefore determined to be 30 mg/m2 and a total of 15 pts were enrolled at this level. The overall response rate was 64% (95% C1:43% 82%) and for the expanded cohort 60% (C1:32% - 84%). The estimated 1year survival for all pts was 71%, and for the expanded cohort also 71%. 3 pts developed pectoral muscle injury in the radiation field, including one biopsy proven necrosis. Conclusions: Paclitaxel can be safely given twice weekly with radical RT (60 Gy) and weekly cisplatin 20 mg/m 2 at a dose of 30 mg/mE Ref: (1) Joschko et al, Rad Oncol Invest 1997; 4: 268. 886
Poster
Induction chemotherapy (CT) followed by concurrent Cisplatin and accelerated radiotherapy in locally advanced nons m a l l cell lung cancer (NSCLC)
R. Arriaqada, S. Kleinman, L. Orlandi, B. Roth 1, C. del Castillo, J. Gutierrez, M. Zuniga, R. Baeza IRAM CBLA-IO0 investigators, GOCCHI Instituto Radiomedicina, Radiation Oncology Department, Santiago, Chile This multicentric phase II trial combined three treatment strategies for locally advanced NSCLC in a total treatment time of 100 days: 1) three courses of induction CT; 2) continuous hyperfractionated accelerated radiotherapy without week-end (CHARTWEL) with 3) concurrent use of daily cisplatin (6 mg/m2).Cycles of CT consisted of cisplatin 100 mg/m 2all, vinorelbi'ne(1 ) 25 mg/m 2 dl, 8, 15 or 22. CHARTWEL delivered a total radiation dose of 54 Gy in 36 fractions and t6 days. The aim of the trial was to evaluate feasibility, considering acceptable a 20% rate of grade Ill-IV esophagitis. The second objective was to measure complete remission (CR) rate after d190. Fifty patients were included, 48 fully evaluated for tumor response or dying before evaluation as of 2002/03/30. Patient characteristics, mean age 60, 3% males, 73% stage IIIB. 75% received the intended treatment. Esophagitis grade Ill-IV was 17% (95%, CI: 7-33). One patient died of toxicity after CT. Tumor response ratese (%) are shown in table (denominator is always 48): Tumour response after CT after CHARTWEL CR 2 31 (CI: 9-46) PR > 50% 52 25 (CI: 4-40) No change 25 12 Progression 12 27 Non assessable 8 4 Objective response rate was 56% (CI: 41-70). Five patients underwent surgery after the protocol, one is a long-term survival (more than 3 years). Mean survival is 21 (CI: 15-27) months. Overall survival rates at 1, 2 and 3 years are 48%, 28 and 19%. This new combined treatment modality is feasible, and may allow a wide range of combinations with potential new cytotoxics and a CHARTWEL radical approach for locally advanced NSCLC. (1) In chile, NavelbeneTM was freely provided by Pierre Fabre Oncologie, France. 887 Poster P h a s e II study of concurrent radiochemotherapy (RCT) with
CPT-11/cisplatin in patients (pts) with advanced non small cell lung cancer (NSCLC) G. Klautke 1, R. Fietkau 1, U. Dietrich 1, A. Bier2, P. Ketteret3, A. Thierbach 3 1Department of Radiotherapy, University of Rostock, Rostock, Germany 2Department of Internal Medicine, University of Rostock, Restock, Getmany 3Department of Internal Medicine, Klinikum Suedstadt of Rostock, Rostock, Germany Purpose: The combination of CPT-11 and cis-platin is highly effective against NSCLC and both show synergistic effects with radiation. To assess the efficacy and tocicity of concurrent RCT with cis-platin and CPT - 11 a phase II study was performed. Methods: From 10/98 to 12/01 36 pts (median age64,5 y; Range 49 - 75y) with inoperable or advanced NSCLC (I/115 pts; Ilia 7 pts; IIIB 19 pts; local recurrences 4pts) were treated with conventional fractionated radiation therapy of the macroscopic tumour regions up to 63Gy and the mediastinum up to 45/50,4 Gy. Chemotherapy consisted of CPT-tl 40 mg/m = day