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154 Weekly chemotherapy with alternating non-cross resistant chemotherapy regimens in good-prognosis small cell lung cancer (SCLC). (Final results)
42 (1541
Weekly chemotherapy with alternating non-cross resistant chemotherapy regimens in good-prognosis small cell lung cancer (SCLC). (Final results)
D. Skarlos, E. Samantas, N. Pavlidis, G. Klouvas, C. Kalofonos, E. Panousaki, E. Tsiakopoulos, N. Poulakis, G. Fountzilas. HeCOG Office, Athens, Greece
Data
Twenty-nine pts with good prognosis SCLC, i.e. limited disease (LD) and extensive disease (ED) with good PS (ECOG 0.1) with normal serum sodium, albumine and an alkaline phosphatase less than 1.5 times the upper normal limits, were treated with carboplatin 150 mg/m* I.V. d 1, 15, 29, 43, 57, 71 and etoposide 75 mg/m21.V. d 1-2, 15-16, 29-30, 43-44, 57-58, 71-72 alternating with epirubicin 30 mg/m* I.V. d 8, 22, 36, 50, 63, 77 and ifosfamide 2 gr/m2 (with Mesna protection) on the same days as epirubicin. Complete responders were also given thoracic and prophylactic cranial irradiation therapy, (Group A). Thirty-seven consecutive pts with similar characteristics were further treated as above with a 25% increase of all drugs except for etoposide which was given 75 mg/ms but for 3 consecutive days (Group B). Prophylactic G-CSF administration was given in pts of Group B. Results: (Group A vs Group B) a) Response (OR 79.5% vs 92%, CR 28.6% vs 46.9%) b) TTP 5.74 (1.67-27.34) vs 7.05 (1.18 vs 16.1) months c) survival 8.33 (23-34.66) vs 10.16 94.3-29.94) months. No statistically significant differences for these parameters were found between these two groups. d) Toxicity (WHO Grade 3 and 4): Anaemia 3% vs 23%, neutropenia 0% vs 3%, thrombocytopenia 3% vs IO%, febrile neutropenia 0%-3%. Alopecia was universal. Conclusions: The above weekly regimens, although active and well tolerated, do not seem superior to standard treatment of SCLC.
155 L-l
What is the optimal administration date of lenograstim after myelosupressive chemotherapy (CT) for small cell lung cancer (SCLC): First results of a pilot study
Th. Urban’, D. Paillotin*, J.M. Brechot3, B. Milleron4. P. Clouet5, M.P. Schuller 5, B. Lebeau ‘. ’ Hopita/ St-Antoine, 75012 Paris; *Hbpifa/ de Boisguillaume, 76230 Boisguillaume; 3 /#pita/ H&e/-Dieu, 75004 Paris; 4 l&pita/ Tenon, 75020 Paris; 5 LaboratoireRhBne-Poulenc Rarer. 92454 Montrouge, France
Purpose: To assess the safety of delayed administration of lenograstim at day 6 (D6) or day 9 (D9) after a myelosuppressive CT for SCLC. Patients and Methods: 21 patients (pts) with SCLC were entered in an open label randomized phase II study with cross-over. All pts received a PCDE-regimen (Cisplatin 100 mg/m2 IV Di, Cytoxan 1000 mg/m2 IV Dl, Doxorubicin 45 mg/m* IV Dl, Etoposide 150 mg/m*IV Di-2), administered every 4 weeks for at least 2 cycles. Pts were randomized either into group 6/9 (G6/9), which received lenograstim (263 fig/d SC) at D8 of the first cycle of CT, and at D9 of the second cycle, or group 9/6 (G9/6) which proceeded inversely. Primary end-point was Time to Neutrophil Recovery (TNR) after Dl. No dose reduction was allowed. Results: 7 pts were withdrawn from the study after the first cycle (2 pts due to toxic death, 5 due to dose reduction following grade 4 hematological toxicity). 5i7 were into G6/9. TNR was studied both with CMH test for the first cycle of chemotherapy, and with cross-over test for the two cycles. Results are summarized in the table below:
Median TNR (days) Median davof nadir
G 619
G 916
Cross-over
G 619
G 916
(fl=7)
(rl=7)
(ll=14)
(rl=ll)
(n=10)
p (CMH test) (n=21)
14 -
15 -
0.0018 -
13 0
15 12
0.048 0.001
50% of pts who received lenograstim at D9 experienced grade 3-4 neutropenia at D9, while none of them had such events when lenograstim was administered at D6. Conclusion: Administration of lenograstim on D6 appears to be safe. The further step is to compare Dl and D6 administration.
11561 Phase II study of docetaxel (Taxotere@) in 1 st and 2nd line NSCLC G. Robinet ‘, J.P. Kleisbauer r, P. Thomas ‘, M. Perol ’ , P. Carles D. Paillotin ‘, H. Lena ’ , R. Poirier ‘, P. Clouet 2, S. Lenseigne *, J.A. Soares’. ’ GFPC (Groupe Frangais de Pneumo-Candrologie); * Laboratoires Rh&e -Poulenc Rarer, France
r,
We performed an open multicenter phase II trial in order to confirm the activity of Taxoterem (TXT) in NSCLC, either as 1st or 2nd line therapy. Eligible patients (pts) had histologically proven locally advanced or metastatic NSCLC, measurable bidimensionnal tumor, no previous chemotherapy (group A) or a maximum of 1 prior platinum-containing chemotherapy for advanced or metastatic disease (group s), PS 52, age 575, normal hematological, hepatic and renal functions, no brain or leptomeningeal involvement and signed informed consent. TXT 100 mg/m*, was administered by 1 h IV infusion, q3w, with premeditation: 5 days oral steroids beginning the day before infusion and continuous diosmine (2 g/day P.O.) from day 1 until the end of study treatment. Ninety-seven pts have been included: 70 in gr. A and 27 in gr. B. The M/F ratio was 85/12; median age 61 (37-74); median PS 1 (O-2); nb of tumor sites: 1 (11%) 2 (33%) ~3 (56%). disease locations: lung/pleura (70%) mediastin (59%), bone (34%) liver (27%) lymph nodes (15%) other locations (19%). Histology: epidermoid (61%), adenocarcinoma (29%) undifferentiated (10%). Prior surgery 27%; prior radiotherapy 23%; prior chemotherapy 28% (gr. 6). Results: 429 cycles (cy) were administered, 80% at 100 mgIms (18% at 75 mg/m* and 3% at 55 mg/ms), median nb of cy: 5 (range l-12). On pts evaluable for response: gr. A (n = 54) overall response rate 31% (95% Cl: 19-45): CR 2%; PR 29%; gr. B (n = 18) overall response rate 22% (95% Cl: 6-48) all PRs. Median duration of response was 7.1 months and the median TTP 4 months. WHO grade 3 and 4 toxicities were (% of 399 eval. cy): grade 3 neutropenia 28% and 22% grade 4; febrile neutropenia 5% (16% of pts); nausea and vomiting 1%; diarrhea 1%. Moderate peripheral edema was seen in 18% of pts (no grade 3 and no pt went off study for severe edema), pleural effusion in 2% and pericardial effusion in 2%. Sensitive neurotoxicity grade 2 was reported in 4.5% of pts (no grade 3/4); 1 pt presented a neuromotor toxicity of grade 2. In this trial, we confirmed that TXT obtains very interesting response rates as 1st (31%) or 2nd line (22%) chemotherapy for NSCLC, with an acceptable toxicity profile.
1
Phase II trial of vinorelbine (NVB) and cisplatin (CDDP) in stage III-IV non-small cell lung cancer (NSCLC)
M. Pawlicki’, K. Krawczyk2, J. Zych3, A. Kowa14, J. Rolski ‘, E. Rowinska-Zakrzewska 3, J.P. Burillon 5, P. Dane1 s, S. Maj 6, F.M. Delgado 5, F. Le Bras 5. ’ Oncology Center, Krakow; ‘J. Paul /I Hospital, Krakow; 31nstitute for Tuberculosis & Lung Disease, Warsaw; 4 Medical Academy Bialistock; 6 Institute of Haernafo/ogM Warsaw, Poland, 51nstitut de Recherche Pierre Fabre, France In the last few years new drugs with promising activity have been identified for the treatment of NSCLC, and of these, NVB has already been shown to increase survival rate in randomised trials. NVB and cisplatin results in statistically superior survival compared with standard therapy (Le Chevalier, JCO 1994; SWOG, Asco 1996). Based on these results, a phase II study was conducted in Poland in order to assess a new schedule of this combination designed to make outpatient administration easier: NVB 30 mg/m* on day 1 & 5 and CDDP 20 mg/m2 daily over 5 days (day 1 to 5) every 21 days, for a maximum of 8 cycles. Forty two patients (pts) were included between February 1995 and February 1996. Forty pts are evaluable for response and tolerance and have the following characteristics: median age 61 (45-74). 76% PS O-l; 66.7% squamous cell carcinoma, 31% adenocarcinoma and 2.3% large cell carcinoma: 57.2% stage IIIB and 33.3% stage IV (9.5% missing data). 180 courses (median 4 range l-8) have been administered. Nine episodes of WHO Grade 3-4 neutropenia were observed in 21.4% of pts. The incidence of infection was low (Grade 3:10% of patients). Grade 3 nausea/vomiting was seen in 10% of pts only. 10% of pts developed WHO Grade 3 constipation and Grade 3-4 peripheral neuropathy was observed in 2.5% of patients. 37.5% of patients developed Grade 2-3 alopecia. Other side effects were uncommon. The overall response rate was 488% (95 Cl 39.4%-71.8%) for a median response duration of 8.8 months. The median survival was 12.2 months (0.6+-25.5+).
Weekly chemotherapy with alternating non-cross resistant chemotherapy regimens in good-prognosis small cell lung cancer (SCLC). (Final results)
D. Skarlos, E. Samantas, N. Pavlidis, G. Klouvas, C. Kalofonos, E. Panousaki, E. Tsiakopoulos, N. Poulakis, G. Fountzilas. HeCOG Office, Athens, Greece
Data
Twenty-nine pts with good prognosis SCLC, i.e. limited disease (LD) and extensive disease (ED) with good PS (ECOG 0.1) with normal serum sodium, albumine and an alkaline phosphatase less than 1.5 times the upper normal limits, were treated with carboplatin 150 mg/m* I.V. d 1, 15, 29, 43, 57, 71 and etoposide 75 mg/m21.V. d 1-2, 15-16, 29-30, 43-44, 57-58, 71-72 alternating with epirubicin 30 mg/m* I.V. d 8, 22, 36, 50, 63, 77 and ifosfamide 2 gr/m2 (with Mesna protection) on the same days as epirubicin. Complete responders were also given thoracic and prophylactic cranial irradiation therapy, (Group A). Thirty-seven consecutive pts with similar characteristics were further treated as above with a 25% increase of all drugs except for etoposide which was given 75 mg/ms but for 3 consecutive days (Group B). Prophylactic G-CSF administration was given in pts of Group B. Results: (Group A vs Group B) a) Response (OR 79.5% vs 92%, CR 28.6% vs 46.9%) b) TTP 5.74 (1.67-27.34) vs 7.05 (1.18 vs 16.1) months c) survival 8.33 (23-34.66) vs 10.16 94.3-29.94) months. No statistically significant differences for these parameters were found between these two groups. d) Toxicity (WHO Grade 3 and 4): Anaemia 3% vs 23%, neutropenia 0% vs 3%, thrombocytopenia 3% vs IO%, febrile neutropenia 0%-3%. Alopecia was universal. Conclusions: The above weekly regimens, although active and well tolerated, do not seem superior to standard treatment of SCLC.
155 L-l
What is the optimal administration date of lenograstim after myelosupressive chemotherapy (CT) for small cell lung cancer (SCLC): First results of a pilot study
Th. Urban’, D. Paillotin*, J.M. Brechot3, B. Milleron4. P. Clouet5, M.P. Schuller 5, B. Lebeau ‘. ’ Hopita/ St-Antoine, 75012 Paris; *Hbpifa/ de Boisguillaume, 76230 Boisguillaume; 3 /#pita/ H&e/-Dieu, 75004 Paris; 4 l&pita/ Tenon, 75020 Paris; 5 LaboratoireRhBne-Poulenc Rarer. 92454 Montrouge, France
Purpose: To assess the safety of delayed administration of lenograstim at day 6 (D6) or day 9 (D9) after a myelosuppressive CT for SCLC. Patients and Methods: 21 patients (pts) with SCLC were entered in an open label randomized phase II study with cross-over. All pts received a PCDE-regimen (Cisplatin 100 mg/m2 IV Di, Cytoxan 1000 mg/m2 IV Dl, Doxorubicin 45 mg/m* IV Dl, Etoposide 150 mg/m*IV Di-2), administered every 4 weeks for at least 2 cycles. Pts were randomized either into group 6/9 (G6/9), which received lenograstim (263 fig/d SC) at D8 of the first cycle of CT, and at D9 of the second cycle, or group 9/6 (G9/6) which proceeded inversely. Primary end-point was Time to Neutrophil Recovery (TNR) after Dl. No dose reduction was allowed. Results: 7 pts were withdrawn from the study after the first cycle (2 pts due to toxic death, 5 due to dose reduction following grade 4 hematological toxicity). 5i7 were into G6/9. TNR was studied both with CMH test for the first cycle of chemotherapy, and with cross-over test for the two cycles. Results are summarized in the table below:
Median TNR (days) Median davof nadir
G 619
G 916
Cross-over
G 619
G 916
(fl=7)
(rl=7)
(ll=14)
(rl=ll)
(n=10)
p (CMH test) (n=21)
14 -
15 -
0.0018 -
13 0
15 12
0.048 0.001
50% of pts who received lenograstim at D9 experienced grade 3-4 neutropenia at D9, while none of them had such events when lenograstim was administered at D6. Conclusion: Administration of lenograstim on D6 appears to be safe. The further step is to compare Dl and D6 administration.
11561 Phase II study of docetaxel (Taxotere@) in 1 st and 2nd line NSCLC G. Robinet ‘, J.P. Kleisbauer r, P. Thomas ‘, M. Perol ’ , P. Carles D. Paillotin ‘, H. Lena ’ , R. Poirier ‘, P. Clouet 2, S. Lenseigne *, J.A. Soares’. ’ GFPC (Groupe Frangais de Pneumo-Candrologie); * Laboratoires Rh&e -Poulenc Rarer, France
r,
We performed an open multicenter phase II trial in order to confirm the activity of Taxoterem (TXT) in NSCLC, either as 1st or 2nd line therapy. Eligible patients (pts) had histologically proven locally advanced or metastatic NSCLC, measurable bidimensionnal tumor, no previous chemotherapy (group A) or a maximum of 1 prior platinum-containing chemotherapy for advanced or metastatic disease (group s), PS 52, age 575, normal hematological, hepatic and renal functions, no brain or leptomeningeal involvement and signed informed consent. TXT 100 mg/m*, was administered by 1 h IV infusion, q3w, with premeditation: 5 days oral steroids beginning the day before infusion and continuous diosmine (2 g/day P.O.) from day 1 until the end of study treatment. Ninety-seven pts have been included: 70 in gr. A and 27 in gr. B. The M/F ratio was 85/12; median age 61 (37-74); median PS 1 (O-2); nb of tumor sites: 1 (11%) 2 (33%) ~3 (56%). disease locations: lung/pleura (70%) mediastin (59%), bone (34%) liver (27%) lymph nodes (15%) other locations (19%). Histology: epidermoid (61%), adenocarcinoma (29%) undifferentiated (10%). Prior surgery 27%; prior radiotherapy 23%; prior chemotherapy 28% (gr. 6). Results: 429 cycles (cy) were administered, 80% at 100 mgIms (18% at 75 mg/m* and 3% at 55 mg/ms), median nb of cy: 5 (range l-12). On pts evaluable for response: gr. A (n = 54) overall response rate 31% (95% Cl: 19-45): CR 2%; PR 29%; gr. B (n = 18) overall response rate 22% (95% Cl: 6-48) all PRs. Median duration of response was 7.1 months and the median TTP 4 months. WHO grade 3 and 4 toxicities were (% of 399 eval. cy): grade 3 neutropenia 28% and 22% grade 4; febrile neutropenia 5% (16% of pts); nausea and vomiting 1%; diarrhea 1%. Moderate peripheral edema was seen in 18% of pts (no grade 3 and no pt went off study for severe edema), pleural effusion in 2% and pericardial effusion in 2%. Sensitive neurotoxicity grade 2 was reported in 4.5% of pts (no grade 3/4); 1 pt presented a neuromotor toxicity of grade 2. In this trial, we confirmed that TXT obtains very interesting response rates as 1st (31%) or 2nd line (22%) chemotherapy for NSCLC, with an acceptable toxicity profile.
1
Phase II trial of vinorelbine (NVB) and cisplatin (CDDP) in stage III-IV non-small cell lung cancer (NSCLC)
M. Pawlicki’, K. Krawczyk2, J. Zych3, A. Kowa14, J. Rolski ‘, E. Rowinska-Zakrzewska 3, J.P. Burillon 5, P. Dane1 s, S. Maj 6, F.M. Delgado 5, F. Le Bras 5. ’ Oncology Center, Krakow; ‘J. Paul /I Hospital, Krakow; 31nstitute for Tuberculosis & Lung Disease, Warsaw; 4 Medical Academy Bialistock; 6 Institute of Haernafo/ogM Warsaw, Poland, 51nstitut de Recherche Pierre Fabre, France In the last few years new drugs with promising activity have been identified for the treatment of NSCLC, and of these, NVB has already been shown to increase survival rate in randomised trials. NVB and cisplatin results in statistically superior survival compared with standard therapy (Le Chevalier, JCO 1994; SWOG, Asco 1996). Based on these results, a phase II study was conducted in Poland in order to assess a new schedule of this combination designed to make outpatient administration easier: NVB 30 mg/m* on day 1 & 5 and CDDP 20 mg/m2 daily over 5 days (day 1 to 5) every 21 days, for a maximum of 8 cycles. Forty two patients (pts) were included between February 1995 and February 1996. Forty pts are evaluable for response and tolerance and have the following characteristics: median age 61 (45-74). 76% PS O-l; 66.7% squamous cell carcinoma, 31% adenocarcinoma and 2.3% large cell carcinoma: 57.2% stage IIIB and 33.3% stage IV (9.5% missing data). 180 courses (median 4 range l-8) have been administered. Nine episodes of WHO Grade 3-4 neutropenia were observed in 21.4% of pts. The incidence of infection was low (Grade 3:10% of patients). Grade 3 nausea/vomiting was seen in 10% of pts only. 10% of pts developed WHO Grade 3 constipation and Grade 3-4 peripheral neuropathy was observed in 2.5% of patients. 37.5% of patients developed Grade 2-3 alopecia. Other side effects were uncommon. The overall response rate was 488% (95 Cl 39.4%-71.8%) for a median response duration of 8.8 months. The median survival was 12.2 months (0.6+-25.5+).