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Navelbine + ifosfamide + cisplatin (NIP) in locally advanced NSCLC
s25
Abstracts
chemotherapy is crucial. The goal of NCI is to eradicate disseminated micrometastases. In the Goldie and Coldman theory, multidrug resistance appears by mutation and randomly. The best probability to avoid this event is provided by the use of systemic therapy as soon as possible in the therapeutic strategy. Phase II studies of neo-adjuvant chemotherapy were conclusive and allowed the step of phase III trials. At the present time, two randomised studies were published by Rose11 et al. and by Roth et al. Both had included a small number of patients (pts): 60 in each trial and they were inconclusive despite positive results. In the Rose11 study, the NCT was mitomycin-ifosfamide-DDP (MIP) for three cycles and in the 2nd, cyclophosphamide-VP16-DDP (two cylces). In both studies, inclusion criteria consisted of stage IIIa tumors. A 3rd trial was directed by the CALGB and was promptly interrupted for lack of inclusion. The NCI was DDP-VP16 (two cycles). Median survival durations were not different. A French randomised study was conducted from 1991 to 1997 and compared two different strategies, one consisted of surgery alone and the other included neoadjuvant chemotherapy followed by surgery. Three hundred and seventy-two pts were included from 38 institutions. Patients with stage I (except for TlNO), II and resectable IIIa NSCLC could be included. The NCT was MIP (two cycles before surgery and two other cycles after surgery if an OR was observed). The preliminary results confirmed the phase II studies’ conclusions: the OR rate was approximately 70%, higher than in stage IV disease; the pathological complete response rate was 11.7%; the progression rate during initial chemotherapy was low, inferior to 5% and impeded surgery in only three cases; the surgical morbidity and mortality were acceptable even if they were higher than expected from the results of the phase II trials. The goal of this trial was an improvement in 2-year survival with an expected rate of 40% in the surgery alone arm and the results will soon be published. Navelbine + ifosfamide + cisplatin (NIP) in locally advanced NSCLC Gottfried M, Yelin A, Shapira Y, Todesco S, Campello VM, Rozenman Y, Brenner HJ. Tel Hashomer, IsraZl. This clinical trial was performed in a neoadjuvant setting for locally advanced NSCLC. The primary measures of evaluation were clinical and histological response rate (RR), time to progression, survival and tolerance. Three induction cycles of N 25 mg/m’ on day 1 and 5, P 80 mg/m* on day 1 and IFOS/MESNA 3 g/m* day 1 every 21-days were administered. Between 06/95 and 09/97, 32 pts have been included. There are 31 pts evaluable for tolerance and response, (one pt ineligible, stage IV): 25 males and six females, median age 56 years (40-75 years); PSO: 52% PSl: 48%. T3 NO: 36%; T2 or 3 N2: 58% T4 NO: 6%. All pts who were node positive on chest CT scan had mediastinoscopy before entering the study to confirm the extent of disease. Tolerance: A total of 92 evaluable courses have been administered; median number of courses: 3 (2-3). The maximal toxicities observed were: febrile neutropenia requiring 48 h hospitalisation (G4): 13%. G2 anaemia: 14% of pts. There was G3 alopecia in 26/31 pts, 12
pts and one pt had G2 and G3 emesis respectively. Results: 18 pts achieved partial response, one pt complete response. The overall response rate was 61%, 29% had stable disease and 10% (all: T3N2) progressed. (80%) 25 pts underwent surgery and among the 13 pts with mediastinal lymph node involvement, confirmed by mediastinoscopy, 10 pts (77%) were downstaged (node negative) histologically confirmed. The median time to progression is estimated at 40 weeks, 1 year survival: 65% and overall survival is not reached, so far. This study confirms that NIP is well tolerated and is a useful neoadjuvant therapy providing favorable results in the management of locally advanced NSCLC. This trial is still ongoing and the next step will be a randomised phase III study to evaluate adjuvant therapy after this induction combination. Induction chemotherapy in stage IIL4/B non-small cell lung cancer (NSCLC): response rates, pattern of relapse, survival times Miiller A, Drings P, Manegold C. Thoraxklinik der LVA Baden, 69126 Heidelberg-Rohrbach,
Germany.
From December 1994 to November 1996, 42 patients (pts) (38 male, four female) with non-small cell lung cancer (NSCLC) stage IIIA (14 pts) or IIIB (28 pts), median age 56 years (range 30-671, and histologically confirmed NSCLC (23 squamous carcinoma, 19 adenocarcinoma) were treated with induction chemotherapy (ICT). Mediastinoscopy was performed routinely. Chemotherapy consisted of 2-4 cycles of cisplatin (90 mg/m’), ifosfamide (6 g/m’) and etoposide (360 mg/m*) given in 3-week intervals. Surgery was carried out in case of tumour response or no change after ICI’, and was followed by radiotherapy if indicated. A partial response was obtained in 47% of pts. In 29 pts surgical resection was performed 3-5 weeks after the last cycle of ICT. RO resection was found in 23 pts (79%0), Rl resection in two pts and R2 resection in four pts. With a median follow up of 15 months, 27 pts (64%) have relapsed. Analysis of relapsed patients showed: (1) relapse occurred mainly in pts with preoperative stage IIIB (IIIA: six pts, IIIB: 21 pts). (2) There is a high percentage of locoregional relapses (eight pts), and locoregional relapse was only seen in stage IIIB. (3) There is a high incidence of brain metastases as only site of relapse (nine pts). Median survival time and 2-year survival was 26.6 months and 54% for pts with response to ICI and subsequent tumour resection, and 11.1 months and < 10% for pts without response to ICT and no tumour resection. Our results indicate that multimodality treatment strategies may be of limited value in stage IIIB NSCLC, and that PC1 should be made a part of multimodality treatment. Neo-adjuvant chemotherapy diotherapy in patients with cancer (NSCLC), preliminary Schramel’ F, Pits’ C, Brute1 H, Biesma4 B, Schlosser’ N,
followed by surgery and/or rastage IIIB non-small cell lung data de la Riviere’ A, Hage’ R, Dik3 Hofman’ P. Dept. Pubnonology/
Cardiovascular Surgery, St. Antonim Hospital Nieuwegein’,‘, Rijnland Ziekenhuis, Leiderdorp3, Bosch Medicentrum, Den Bosch4, University Hospital lJtrecht5, Dept. of Radiotherapy, Universiw Hospital Utrecht 6, the Netherlands.
Abstracts
chemotherapy is crucial. The goal of NCI is to eradicate disseminated micrometastases. In the Goldie and Coldman theory, multidrug resistance appears by mutation and randomly. The best probability to avoid this event is provided by the use of systemic therapy as soon as possible in the therapeutic strategy. Phase II studies of neo-adjuvant chemotherapy were conclusive and allowed the step of phase III trials. At the present time, two randomised studies were published by Rose11 et al. and by Roth et al. Both had included a small number of patients (pts): 60 in each trial and they were inconclusive despite positive results. In the Rose11 study, the NCT was mitomycin-ifosfamide-DDP (MIP) for three cycles and in the 2nd, cyclophosphamide-VP16-DDP (two cylces). In both studies, inclusion criteria consisted of stage IIIa tumors. A 3rd trial was directed by the CALGB and was promptly interrupted for lack of inclusion. The NCI was DDP-VP16 (two cycles). Median survival durations were not different. A French randomised study was conducted from 1991 to 1997 and compared two different strategies, one consisted of surgery alone and the other included neoadjuvant chemotherapy followed by surgery. Three hundred and seventy-two pts were included from 38 institutions. Patients with stage I (except for TlNO), II and resectable IIIa NSCLC could be included. The NCT was MIP (two cycles before surgery and two other cycles after surgery if an OR was observed). The preliminary results confirmed the phase II studies’ conclusions: the OR rate was approximately 70%, higher than in stage IV disease; the pathological complete response rate was 11.7%; the progression rate during initial chemotherapy was low, inferior to 5% and impeded surgery in only three cases; the surgical morbidity and mortality were acceptable even if they were higher than expected from the results of the phase II trials. The goal of this trial was an improvement in 2-year survival with an expected rate of 40% in the surgery alone arm and the results will soon be published. Navelbine + ifosfamide + cisplatin (NIP) in locally advanced NSCLC Gottfried M, Yelin A, Shapira Y, Todesco S, Campello VM, Rozenman Y, Brenner HJ. Tel Hashomer, IsraZl. This clinical trial was performed in a neoadjuvant setting for locally advanced NSCLC. The primary measures of evaluation were clinical and histological response rate (RR), time to progression, survival and tolerance. Three induction cycles of N 25 mg/m’ on day 1 and 5, P 80 mg/m* on day 1 and IFOS/MESNA 3 g/m* day 1 every 21-days were administered. Between 06/95 and 09/97, 32 pts have been included. There are 31 pts evaluable for tolerance and response, (one pt ineligible, stage IV): 25 males and six females, median age 56 years (40-75 years); PSO: 52% PSl: 48%. T3 NO: 36%; T2 or 3 N2: 58% T4 NO: 6%. All pts who were node positive on chest CT scan had mediastinoscopy before entering the study to confirm the extent of disease. Tolerance: A total of 92 evaluable courses have been administered; median number of courses: 3 (2-3). The maximal toxicities observed were: febrile neutropenia requiring 48 h hospitalisation (G4): 13%. G2 anaemia: 14% of pts. There was G3 alopecia in 26/31 pts, 12
pts and one pt had G2 and G3 emesis respectively. Results: 18 pts achieved partial response, one pt complete response. The overall response rate was 61%, 29% had stable disease and 10% (all: T3N2) progressed. (80%) 25 pts underwent surgery and among the 13 pts with mediastinal lymph node involvement, confirmed by mediastinoscopy, 10 pts (77%) were downstaged (node negative) histologically confirmed. The median time to progression is estimated at 40 weeks, 1 year survival: 65% and overall survival is not reached, so far. This study confirms that NIP is well tolerated and is a useful neoadjuvant therapy providing favorable results in the management of locally advanced NSCLC. This trial is still ongoing and the next step will be a randomised phase III study to evaluate adjuvant therapy after this induction combination. Induction chemotherapy in stage IIL4/B non-small cell lung cancer (NSCLC): response rates, pattern of relapse, survival times Miiller A, Drings P, Manegold C. Thoraxklinik der LVA Baden, 69126 Heidelberg-Rohrbach,
Germany.
From December 1994 to November 1996, 42 patients (pts) (38 male, four female) with non-small cell lung cancer (NSCLC) stage IIIA (14 pts) or IIIB (28 pts), median age 56 years (range 30-671, and histologically confirmed NSCLC (23 squamous carcinoma, 19 adenocarcinoma) were treated with induction chemotherapy (ICT). Mediastinoscopy was performed routinely. Chemotherapy consisted of 2-4 cycles of cisplatin (90 mg/m’), ifosfamide (6 g/m’) and etoposide (360 mg/m*) given in 3-week intervals. Surgery was carried out in case of tumour response or no change after ICI’, and was followed by radiotherapy if indicated. A partial response was obtained in 47% of pts. In 29 pts surgical resection was performed 3-5 weeks after the last cycle of ICT. RO resection was found in 23 pts (79%0), Rl resection in two pts and R2 resection in four pts. With a median follow up of 15 months, 27 pts (64%) have relapsed. Analysis of relapsed patients showed: (1) relapse occurred mainly in pts with preoperative stage IIIB (IIIA: six pts, IIIB: 21 pts). (2) There is a high percentage of locoregional relapses (eight pts), and locoregional relapse was only seen in stage IIIB. (3) There is a high incidence of brain metastases as only site of relapse (nine pts). Median survival time and 2-year survival was 26.6 months and 54% for pts with response to ICI and subsequent tumour resection, and 11.1 months and < 10% for pts without response to ICT and no tumour resection. Our results indicate that multimodality treatment strategies may be of limited value in stage IIIB NSCLC, and that PC1 should be made a part of multimodality treatment. Neo-adjuvant chemotherapy diotherapy in patients with cancer (NSCLC), preliminary Schramel’ F, Pits’ C, Brute1 H, Biesma4 B, Schlosser’ N,
followed by surgery and/or rastage IIIB non-small cell lung data de la Riviere’ A, Hage’ R, Dik3 Hofman’ P. Dept. Pubnonology/
Cardiovascular Surgery, St. Antonim Hospital Nieuwegein’,‘, Rijnland Ziekenhuis, Leiderdorp3, Bosch Medicentrum, Den Bosch4, University Hospital lJtrecht5, Dept. of Radiotherapy, Universiw Hospital Utrecht 6, the Netherlands.