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Granulocyte colony stimulating factor (G-CSF) enables dose intensification of chemotherapy in small cell lung cancer (SCLC)
107 406 Intensive weekly treatment with alternating non-cross resistant combination chemotherapy and G-CSF support followed by thoracic and prophylactic cranial irradiation for good prognosis patients with small-cell lung cancer (SCLC).
Granulocyte Colony Stimulating Factor (G-CSF) enables dose intensification of chemotherapy in small Celllung cancer (SCLC). V.Trillet-Lenoir ELP. Soler-Michel for the Groupe Lyonnais d’OncologieThoracique, France.
Skarlos D.V, Samantas E, Pavlidis N, Kalaitzidou E., Polyzogopoulos D, Kalophonos Ch, Loucatou M, Kardamakis D, Klouvas, G, Panousaki E, Makrantonakis P, Tsugranis A, Tsiakopoulos E, Fountzilas G. Hellenic Co-operative Oncology Group (HeCOG) for Lung Cancer (GREECE). Seventy (70) patients (pts) with SCLC and LD or ED with good prognostic features (PS:O-I, normal values of serum sodium, albumin and alkaline phosphatase) were entered this study. The 35 pts were treated with a 12-week duration treatment consisted of carboplatin (150 mg/m” iv dl) and etoposide (75 mg/m’ iv dl-2) alternated with Epirubicin (30 mg/m2 iv dl) and ifosfamide (2 gr/m2) iv dl with Mesna uroprotection (Group A). Cycles were given weekly. G-CSF Sug/kgr/day was also given on d 3-7 of each cycle. The next 35 pts were treated with the same regimen but wlth increased doses of the 3 drugs by 25% while etoposide was given at the same dose for 3 consecutive days (Group B). Pts with LD in CR had also thoracic irradiation (45 Gy in 1.6 daily fractions) and prophylactic cranial irradiation (2.0 Gy in daily fractions). Results (Group A/B): Response overall (46) 66/60, CR (%) 23/37 (p:O.1954) Median time to progression (months): 5.41/6.59 (p:O.3229), median survival (months): 9.97/9.51 (p:O.3205). Toxicity (Group A/B): Grade 3-4: neutropenia(%) (O/29), thrombocytopenia(%) 3/9, nausea(%) (g/3). Alopecia was noticed in almost all pts. The results of this study do not support the use of weekly alternating non-cross resistant chemotherapy in SCLC.
G-CSF allows rapid neutrophils We evaluated chemotherapy
the feasibility in 48 patients
recovery after chemotherapy. of accelerated delivery of (pts) with extensive SCLC.
Treatment consisted of Doxorubicin 50 mglm2 , Etoposide 120 mg/m* X 3 and lfosfamide 2 g/m* x 2 (+ Mesna) given every 2 weeks and followed by G-CSF 5 pg/kg/day SC days 4 to 14. Twenty two pts were withdrawn from the study : 5 severe septic complication (4 of which lethal), 8 grade 4 thrombopenia, 3 patient’s refusal, 6 no response after 3 courses. Out of the 212 analysed courses, 42 had to be delayed (20 for thrombopenia). The mean duration of delays was 5 days. No dose reductions were performed. Optimal dose-on-time administration was feasible in 66% pts for 3 courses, 46% for 4 courses and 23% for 6 courses. The mean actually received dose intensity was 100% of the planned dose at 4 courses and 93% at 6 courses. It was 1.8 times higher than in our previous conventional 3 weeksintervals chemotherapy protocol. The median neutrophils nadirs were stable during the successive treatment courses while haemoglobin and platelets values significantly worsened. The overall response rate was 79% in the 42 evaluable pts. Thrombopenia is the main limiting factor for dose intensification with accelerated chemotherapy. Growth factors active on the megacaryocytic lineage might be usefull in this setting.
409
WEEKLY ADMINISTRATION OF MODERATE DOSES OF CISPLATJN (25 MG/M2) AND CARROPLATIN (100 MG/M2) AS SALVAGE CHEMOTHERAPY MIR SMALL CELL LUNG CANCER. J.P. Sculier, J. Thhiaux, G. Bureau, J.J. Lafitte, P. Recloux, M. Paesmans, P. Mommen and J. Klastersky for the European Lung Cancer Working Party; Institut Jules Bordet, &US&, Belgium. A phase II trial was conducted to determine the effectiveness of weekly administration of cisplatm (25 mglm2 d 1) and carboplatin (100 mg/m2) as salvage chemotherapy for small cell lung cancer after fist line chemotherapy with ifosfamide, etoposide and adriamycin or epirubicin. On 41 registered patients, 31 have been evaluated at time of present report : 2 were not evaluable for response. Mean age was 57 year (range : 40-74); sex was male in 27 and female in 4; Kamofsky PS (not recorded in 5) was < 70 in 10 and 2 80 in 16; disease was limited in 6 and extensive in 25. Interval between last course of fust line chemotherapy and first course of salvage therapy was less than 3 months in 23 and greater in a pts. Four partial responses (14 %) were documented (including 3 in patients with a free-treatment interval < 3 months) as well as 5 no change, 16 progressions and 4 early deaths due to malignant disease. Patients received a median number of 6 courses (range : l-23). Toxicity consisted mainly in moderate leucopenia, tbrombopenia and nausea. Grade I nephrotoxicity was observed in 5 pts. In conclusion, weekly administration of moderate doses of cisplatin and carboplatin as salvage chemotherapy for small cell lung cancer appeared feasable and was associated with a moderate anticancer activity.
EARLY PHASE II SMALL CELL IN
STUDY LUNG
OF VINORELBINE (VNR) CANCER. K. Furuse*, M.
Kawahara, M. Fukuoka, I. Kimura, A. Fujii, M. Oota, A. Sakuma and H. Niitani. Lung Cancer Group of KW-230'7, Japan, Cooperative Study *National Kinki Central Hospitai for Chest Diseases, Sakai, Osaka 591 Japan a novel vinca alkaloid derivative, was shown VNR, to be effective in non-small cell lung cancer and breast cancer in Europe and Japan. ?he maximum tolerated dose was found to be 3Omg/m ;n phase I study in Japan. Puroose: in order to evaluate the activity and toxicity in pts with previously treated small cell lung cancer, phase II study was performed. Methods: VNR was given at a dose of 25mg/m' by intravenous injection and repeated 4 times oz more. Results: All pts were eligible among 24 pts enrolled. The background of pts was as follows: median age 65 years; PSO 20%, PSl 28%. PS2 48%. PS3 4%: male 76%. female 24%: vinca alkaloid treatment 76%. The overall response rate was 12.5% (3/24) (PR 12%. NC 40%, PD 248, NE 24%). All responsive pts were previously treated with vinca alkaloid. The major toxicity was leukopenia and WHO grade 3-4 grade leukopenia develooed in 60 % of 24 eliaible rots. Anorexia (35.7%j, nausea.omiting (35.08). alopecia (23.5%) were observed with incidence over 20%. But these toxicities were mild with WHO grade 2 OI below. WHO Grade 3 toxicity was developed in 1 patient with paresthesia. Conclusion: VNR showed to be effective in pts with recurrent small cell lung vinca cancer and prior alkaioid treatment. Toxicity was mild and tolerable. Further studies on the efficacy of VNR to small cell lung cancer should be conducted in combinatlor, chemotherapy.
Granulocyte Colony Stimulating Factor (G-CSF) enables dose intensification of chemotherapy in small Celllung cancer (SCLC). V.Trillet-Lenoir ELP. Soler-Michel for the Groupe Lyonnais d’OncologieThoracique, France.
Skarlos D.V, Samantas E, Pavlidis N, Kalaitzidou E., Polyzogopoulos D, Kalophonos Ch, Loucatou M, Kardamakis D, Klouvas, G, Panousaki E, Makrantonakis P, Tsugranis A, Tsiakopoulos E, Fountzilas G. Hellenic Co-operative Oncology Group (HeCOG) for Lung Cancer (GREECE). Seventy (70) patients (pts) with SCLC and LD or ED with good prognostic features (PS:O-I, normal values of serum sodium, albumin and alkaline phosphatase) were entered this study. The 35 pts were treated with a 12-week duration treatment consisted of carboplatin (150 mg/m” iv dl) and etoposide (75 mg/m’ iv dl-2) alternated with Epirubicin (30 mg/m2 iv dl) and ifosfamide (2 gr/m2) iv dl with Mesna uroprotection (Group A). Cycles were given weekly. G-CSF Sug/kgr/day was also given on d 3-7 of each cycle. The next 35 pts were treated with the same regimen but wlth increased doses of the 3 drugs by 25% while etoposide was given at the same dose for 3 consecutive days (Group B). Pts with LD in CR had also thoracic irradiation (45 Gy in 1.6 daily fractions) and prophylactic cranial irradiation (2.0 Gy in daily fractions). Results (Group A/B): Response overall (46) 66/60, CR (%) 23/37 (p:O.1954) Median time to progression (months): 5.41/6.59 (p:O.3229), median survival (months): 9.97/9.51 (p:O.3205). Toxicity (Group A/B): Grade 3-4: neutropenia(%) (O/29), thrombocytopenia(%) 3/9, nausea(%) (g/3). Alopecia was noticed in almost all pts. The results of this study do not support the use of weekly alternating non-cross resistant chemotherapy in SCLC.
G-CSF allows rapid neutrophils We evaluated chemotherapy
the feasibility in 48 patients
recovery after chemotherapy. of accelerated delivery of (pts) with extensive SCLC.
Treatment consisted of Doxorubicin 50 mglm2 , Etoposide 120 mg/m* X 3 and lfosfamide 2 g/m* x 2 (+ Mesna) given every 2 weeks and followed by G-CSF 5 pg/kg/day SC days 4 to 14. Twenty two pts were withdrawn from the study : 5 severe septic complication (4 of which lethal), 8 grade 4 thrombopenia, 3 patient’s refusal, 6 no response after 3 courses. Out of the 212 analysed courses, 42 had to be delayed (20 for thrombopenia). The mean duration of delays was 5 days. No dose reductions were performed. Optimal dose-on-time administration was feasible in 66% pts for 3 courses, 46% for 4 courses and 23% for 6 courses. The mean actually received dose intensity was 100% of the planned dose at 4 courses and 93% at 6 courses. It was 1.8 times higher than in our previous conventional 3 weeksintervals chemotherapy protocol. The median neutrophils nadirs were stable during the successive treatment courses while haemoglobin and platelets values significantly worsened. The overall response rate was 79% in the 42 evaluable pts. Thrombopenia is the main limiting factor for dose intensification with accelerated chemotherapy. Growth factors active on the megacaryocytic lineage might be usefull in this setting.
409
WEEKLY ADMINISTRATION OF MODERATE DOSES OF CISPLATJN (25 MG/M2) AND CARROPLATIN (100 MG/M2) AS SALVAGE CHEMOTHERAPY MIR SMALL CELL LUNG CANCER. J.P. Sculier, J. Thhiaux, G. Bureau, J.J. Lafitte, P. Recloux, M. Paesmans, P. Mommen and J. Klastersky for the European Lung Cancer Working Party; Institut Jules Bordet, &US&, Belgium. A phase II trial was conducted to determine the effectiveness of weekly administration of cisplatm (25 mglm2 d 1) and carboplatin (100 mg/m2) as salvage chemotherapy for small cell lung cancer after fist line chemotherapy with ifosfamide, etoposide and adriamycin or epirubicin. On 41 registered patients, 31 have been evaluated at time of present report : 2 were not evaluable for response. Mean age was 57 year (range : 40-74); sex was male in 27 and female in 4; Kamofsky PS (not recorded in 5) was < 70 in 10 and 2 80 in 16; disease was limited in 6 and extensive in 25. Interval between last course of fust line chemotherapy and first course of salvage therapy was less than 3 months in 23 and greater in a pts. Four partial responses (14 %) were documented (including 3 in patients with a free-treatment interval < 3 months) as well as 5 no change, 16 progressions and 4 early deaths due to malignant disease. Patients received a median number of 6 courses (range : l-23). Toxicity consisted mainly in moderate leucopenia, tbrombopenia and nausea. Grade I nephrotoxicity was observed in 5 pts. In conclusion, weekly administration of moderate doses of cisplatin and carboplatin as salvage chemotherapy for small cell lung cancer appeared feasable and was associated with a moderate anticancer activity.
EARLY PHASE II SMALL CELL IN
STUDY LUNG
OF VINORELBINE (VNR) CANCER. K. Furuse*, M.
Kawahara, M. Fukuoka, I. Kimura, A. Fujii, M. Oota, A. Sakuma and H. Niitani. Lung Cancer Group of KW-230'7, Japan, Cooperative Study *National Kinki Central Hospitai for Chest Diseases, Sakai, Osaka 591 Japan a novel vinca alkaloid derivative, was shown VNR, to be effective in non-small cell lung cancer and breast cancer in Europe and Japan. ?he maximum tolerated dose was found to be 3Omg/m ;n phase I study in Japan. Puroose: in order to evaluate the activity and toxicity in pts with previously treated small cell lung cancer, phase II study was performed. Methods: VNR was given at a dose of 25mg/m' by intravenous injection and repeated 4 times oz more. Results: All pts were eligible among 24 pts enrolled. The background of pts was as follows: median age 65 years; PSO 20%, PSl 28%. PS2 48%. PS3 4%: male 76%. female 24%: vinca alkaloid treatment 76%. The overall response rate was 12.5% (3/24) (PR 12%. NC 40%, PD 248, NE 24%). All responsive pts were previously treated with vinca alkaloid. The major toxicity was leukopenia and WHO grade 3-4 grade leukopenia develooed in 60 % of 24 eliaible rots. Anorexia (35.7%j, nausea.omiting (35.08). alopecia (23.5%) were observed with incidence over 20%. But these toxicities were mild with WHO grade 2 OI below. WHO Grade 3 toxicity was developed in 1 patient with paresthesia. Conclusion: VNR showed to be effective in pts with recurrent small cell lung vinca cancer and prior alkaioid treatment. Toxicity was mild and tolerable. Further studies on the efficacy of VNR to small cell lung cancer should be conducted in combinatlor, chemotherapy.