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Longer survival with higher doses of thoracic radiotherapy in non small cell lung cancer (NSCLC)
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EFFICACITYOF CARBOPLATIN IN BRAIN METASTASIS OF LUNG CANCER. B. Velay for
the Group Lyonnais d'0ncologie Thoracique. BP : ARISTOT Facultede Wdecine de Lyon 8, avenue Rockefeller69008 LYON France. Carboplatin has similar activity to cisplatin in human lung cancer but the animal experimentation show a better cerebral concentration. Between Q/1988 and 03/1990 17 patients (all men, mean age 58 years) were included in a phase II trial of Carboplatin in monotherapy 600 mg/m2 Jl-J28 in brain metastasis of Lung The evaluation (clinical examination and Cancer. tomodensitometry) was performed one month after the second course. All the patients have an histologically proved lung cancer with brain metastasis : 10 Small Cell Lung Cancer (SCLC) with brain evolution after conventional chemotherapy (without brain irradiation and previous cisplatin) and 7 Non Small Cell : 15 paLung Cancer (NSCLC) no previously treated tients are evaluable for response after 2 courses (2 early deaths by progressive disease outside the The response are as follow 0 CR, 4 PR (1 brain). NSCLC, 3 SCLC), 3 Minor Response (1 NSCLC, 2 SCLC), 1 No Change (SCLC), 7 progression (4 NSCLC, 3 SCLC) : after 4 courses all 5 pa27 % objective response. tients have a brain metastasis progression. The toxicity is mild and only hematological (6 grade II, 3 grade III) ; the median survival is 4 months. Carboplatin has a real efficacity in brain metastasis .but during a short period of time.
CAREOPLATIN, VINELASTIN and MITOMYCIN (CMV) IN ADVANCED AND DISSEMINATED NON SMALL CELL LUNG CANCER (NSCLC) P.J. SOUQUET, P. FOURNEL, GLOT, Groupe Lyonnais d'On cologie Thoracique ARISTOT Faculte de Medecine de Lyon 8, avenue Rockefeller 69008 LYON France Between 06/89 and 06/90, 30 patients with advanced and disseminated NSCLC (14 stage IV, 16 stage 1118, 28 men, mean age 52,6 years, 18 squamous carcinoma, 7 undifferentiated, 5 adenocarcinoma) were included in a phase II trial of Carboplatin (300 mg/m2), Vinblastin (6 mg/mz), Mitomycin C (8 mg/m2) Jl-J29-J57 In stage IV three others courses were performed only
in objective responders and in stage 1116 a X Ray Therapy (XRT)was performed one month after the third course. After three courses of chemotherapy. the respons was as follow : CR : 0, PR > 50 % 5 (17 %), stable disease 4, progression 15, non evaluable 5. In stage IV 1 PR) 50 % after 3 and 6 courses, in stage 1118 4 PR> 50 % and after XRT 1 CR (DFS?2D months) and 5 PR. The median survival was 4 months for stage IV and 7 months for stage 1118. The toxicity was only hematological 1 grade IV (toxic death by pneumonia), 5 grade III, 6 grade II. This schedule of chemotherapy seems to be poorly active in advanced and disseminated NSCLC. This study was supported by a grant of the "Ligue du Rh6ne contre le cancer”.
374
373 lWW4IZED TRIAL OFWfWlATIN
(CEKE4)AND ETWDSIDE (E)
PavlINISTERED EIlHEf?IV IN A THREE-DAYSCHWILE CR IN A KUlWCTEDOR&~ IN KN-WLLCELL LLKGCAEKER (NSCLC). R T&sell,N Ribelles,A Abad, P SxrLabarbwa*,A Bamadas, V Warn, A Fcnt, F Fblina. lhiversity&pita1 emens Trias i Pujol, Badalcna,Barcelcnaand * Bristol-Myers, Madrid.Spain. C8K.A activityin advancedNSCLC varies frur 7% to 2@ accordingto the resultsof four trials.E has shownschedule dependency in its anti-turar effect. To further test the synergisticeffect of CBDCA and E, forty-sevenpatientswith r&astatic or advanced and recurrentmasurable NSCLC were entered into the trial with CBDCA 325 ng/sqn iv and either iv E 100 rrg/sqn on days l-3 or E 50 g/scp /day x 21 days given orally.Courseswere repzatedevery 28 days for six. To date, 35 patients are evaluable for response and toxicity.The madian age of patientswas 57 yrs and 66 yrs in iv
Kamofsky was 80% in both am. In iv arm, there was 1 CR and 6 RR’s (overall 33%response rate). Cc the protracted E arm, there was 1 CR and 3 FR’s (overall 26% resqxnse rate). Non-kretolcgic toxicities here generally graded 1-2, Lut nor-e patients bad medianabsolute nautrophil cc& nadir below loo0 in E protractedarm (28.5%)vs 9.5% in iv E arinand
and oral arm, respectively. klian
also platelet
nadir Mm 99.KQ 35%in oral E vs 9.5% in iv arm. For this less chmmensitive km, the response rate was’mt higher in oral E am in spite of a three-fold increase doseintensity of E being given.
SINGLE AGSHT ORAL PTOPOSIDE IN ADVAWCED llCIC (C4IRDNICDAILY) AND YN DIDDALY PATIEUTB WITE SCLC. U. Gatrumier, R. Neuhauee, II. Neckmayr. Dep. of Thoracic Oncology, Groaahanadocf Eoapital, Hgb., G-=-Y Introduction: Etoposide is one of the most active drugs both in NSCLC and SCLC. The optimal dose and schedule remain undefined Patient8 and %&hods: NSCLC' Up to now 14 Patients with advanced inoperableNSCLC received 100 mg Etoposide orally x 14 days + I days rest period. The study is ongoing up to 25 evaluable patients. ScLc: Elderly and unfit patients were included into the phase II protocoll. Each cycle consisted of a total dose of 500 mg/m2 oral etoposide divided over 3 consecutive days + 8 - 10 days rest period. RBsulte: NSCLC: There were 6 PR out of 14 patients. Prior chemotherapy didn't influence the likelyhood of response to oral E. In general toxicity was mild. ..---.
SCLC: 55 patients were entered into the protocol1 =42/13) Median acre: 75 Y. Staae: LD/ED- 33122. Overall response rati CR + iR: 1l;l % +'46,3 %. MST: LD 7,5 mo., Ed 6,5 mo. Gastrointestinal toxicity was mild. The main haematological side effects were leucocytopenia (WHO 3: 14,8% WHO: ll,l%l thrombocytopenia:(iDiO .3+4:11,2 %) Conclueion: Oral etoposide, chronic daily administered, showed surprising activity in advanced NSCLC without loss of quality of life. Also in SCLC single agent E is an effective therapy in elderly unfit patients.
371
EFFICACITYOF CARBOPLATIN IN BRAIN METASTASIS OF LUNG CANCER. B. Velay for
the Group Lyonnais d'0ncologie Thoracique. BP : ARISTOT Facultede Wdecine de Lyon 8, avenue Rockefeller69008 LYON France. Carboplatin has similar activity to cisplatin in human lung cancer but the animal experimentation show a better cerebral concentration. Between Q/1988 and 03/1990 17 patients (all men, mean age 58 years) were included in a phase II trial of Carboplatin in monotherapy 600 mg/m2 Jl-J28 in brain metastasis of Lung The evaluation (clinical examination and Cancer. tomodensitometry) was performed one month after the second course. All the patients have an histologically proved lung cancer with brain metastasis : 10 Small Cell Lung Cancer (SCLC) with brain evolution after conventional chemotherapy (without brain irradiation and previous cisplatin) and 7 Non Small Cell : 15 paLung Cancer (NSCLC) no previously treated tients are evaluable for response after 2 courses (2 early deaths by progressive disease outside the The response are as follow 0 CR, 4 PR (1 brain). NSCLC, 3 SCLC), 3 Minor Response (1 NSCLC, 2 SCLC), 1 No Change (SCLC), 7 progression (4 NSCLC, 3 SCLC) : after 4 courses all 5 pa27 % objective response. tients have a brain metastasis progression. The toxicity is mild and only hematological (6 grade II, 3 grade III) ; the median survival is 4 months. Carboplatin has a real efficacity in brain metastasis .but during a short period of time.
CAREOPLATIN, VINELASTIN and MITOMYCIN (CMV) IN ADVANCED AND DISSEMINATED NON SMALL CELL LUNG CANCER (NSCLC) P.J. SOUQUET, P. FOURNEL, GLOT, Groupe Lyonnais d'On cologie Thoracique ARISTOT Faculte de Medecine de Lyon 8, avenue Rockefeller 69008 LYON France Between 06/89 and 06/90, 30 patients with advanced and disseminated NSCLC (14 stage IV, 16 stage 1118, 28 men, mean age 52,6 years, 18 squamous carcinoma, 7 undifferentiated, 5 adenocarcinoma) were included in a phase II trial of Carboplatin (300 mg/m2), Vinblastin (6 mg/mz), Mitomycin C (8 mg/m2) Jl-J29-J57 In stage IV three others courses were performed only
in objective responders and in stage 1116 a X Ray Therapy (XRT)was performed one month after the third course. After three courses of chemotherapy. the respons was as follow : CR : 0, PR > 50 % 5 (17 %), stable disease 4, progression 15, non evaluable 5. In stage IV 1 PR) 50 % after 3 and 6 courses, in stage 1118 4 PR> 50 % and after XRT 1 CR (DFS?2D months) and 5 PR. The median survival was 4 months for stage IV and 7 months for stage 1118. The toxicity was only hematological 1 grade IV (toxic death by pneumonia), 5 grade III, 6 grade II. This schedule of chemotherapy seems to be poorly active in advanced and disseminated NSCLC. This study was supported by a grant of the "Ligue du Rh6ne contre le cancer”.
374
373 lWW4IZED TRIAL OFWfWlATIN
(CEKE4)AND ETWDSIDE (E)
PavlINISTERED EIlHEf?IV IN A THREE-DAYSCHWILE CR IN A KUlWCTEDOR&~ IN KN-WLLCELL LLKGCAEKER (NSCLC). R T&sell,N Ribelles,A Abad, P SxrLabarbwa*,A Bamadas, V Warn, A Fcnt, F Fblina. lhiversity&pita1 emens Trias i Pujol, Badalcna,Barcelcnaand * Bristol-Myers, Madrid.Spain. C8K.A activityin advancedNSCLC varies frur 7% to 2@ accordingto the resultsof four trials.E has shownschedule dependency in its anti-turar effect. To further test the synergisticeffect of CBDCA and E, forty-sevenpatientswith r&astatic or advanced and recurrentmasurable NSCLC were entered into the trial with CBDCA 325 ng/sqn iv and either iv E 100 rrg/sqn on days l-3 or E 50 g/scp /day x 21 days given orally.Courseswere repzatedevery 28 days for six. To date, 35 patients are evaluable for response and toxicity.The madian age of patientswas 57 yrs and 66 yrs in iv
Kamofsky was 80% in both am. In iv arm, there was 1 CR and 6 RR’s (overall 33%response rate). Cc the protracted E arm, there was 1 CR and 3 FR’s (overall 26% resqxnse rate). Non-kretolcgic toxicities here generally graded 1-2, Lut nor-e patients bad medianabsolute nautrophil cc& nadir below loo0 in E protractedarm (28.5%)vs 9.5% in iv E arinand
and oral arm, respectively. klian
also platelet
nadir Mm 99.KQ 35%in oral E vs 9.5% in iv arm. For this less chmmensitive km, the response rate was’mt higher in oral E am in spite of a three-fold increase doseintensity of E being given.
SINGLE AGSHT ORAL PTOPOSIDE IN ADVAWCED llCIC (C4IRDNICDAILY) AND YN DIDDALY PATIEUTB WITE SCLC. U. Gatrumier, R. Neuhauee, II. Neckmayr. Dep. of Thoracic Oncology, Groaahanadocf Eoapital, Hgb., G-=-Y Introduction: Etoposide is one of the most active drugs both in NSCLC and SCLC. The optimal dose and schedule remain undefined Patient8 and %&hods: NSCLC' Up to now 14 Patients with advanced inoperableNSCLC received 100 mg Etoposide orally x 14 days + I days rest period. The study is ongoing up to 25 evaluable patients. ScLc: Elderly and unfit patients were included into the phase II protocoll. Each cycle consisted of a total dose of 500 mg/m2 oral etoposide divided over 3 consecutive days + 8 - 10 days rest period. RBsulte: NSCLC: There were 6 PR out of 14 patients. Prior chemotherapy didn't influence the likelyhood of response to oral E. In general toxicity was mild. ..---.
SCLC: 55 patients were entered into the protocol1 =42/13) Median acre: 75 Y. Staae: LD/ED- 33122. Overall response rati CR + iR: 1l;l % +'46,3 %. MST: LD 7,5 mo., Ed 6,5 mo. Gastrointestinal toxicity was mild. The main haematological side effects were leucocytopenia (WHO 3: 14,8% WHO: ll,l%l thrombocytopenia:(iDiO .3+4:11,2 %) Conclueion: Oral etoposide, chronic daily administered, showed surprising activity in advanced NSCLC without loss of quality of life. Also in SCLC single agent E is an effective therapy in elderly unfit patients.