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Pilot study of multi-cyclic combination chemotherapy (MCCCT) for extensive small cell lung cancer (SCLC)
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TNNIPGSIDB FOR BRAIN NBTASTASES OF WALL CELL LUNG CANCER, BORTC PRCTCCGL 08873 piater II. Postmus, Groningen; Nice van Bandwijk, Amsterdam; Andrea Ardirroni, Genus; Elisabeth Quoix, Strassbourg; Anne Kirkpatrick, Brussels and the EORTC LUNG CANCER COOPERATIVE GROUP. Brain metastases is the most devastating form of metastatic disease in SCLC occurring in over 50 % of the patients. Results of cranial radiotherapy are poor partly due to tumor progression outside the CNS, poor Performance Status and lack of machine time. In a previous study high-dose etoposide resulted in CT documented CR's and PR's, but this was associated with severe myelotoxicity and toxic death (Br J Cancer 1989, 5, 524). In this study the congener of eto side, teniposide, was given at a dose of 150 p4 mgfm on day 1, 3, 5 every 3 weeks to patients with brain metastases of SCLC, either at diagnosis (~11) or during treatment or follow-up. Response was evaluated by brain CT after 2, 6 and 12 cycles. Of 81 patients 72 were avaluable for response. Response was: 7 CR, 19 PR, 12 NC, 17 PD, 17 BD/TD (died within 42 days from start). Response rate 36 %. Of these patients survival was (medium (range)): CR 348 days PR 149 (70-393), NC 112 (44-2BO), PD 60 $S;;;~), . Toxicity was almost only hematologic with grade 4 myelotoxicity in 9 % of the courses. We conclude that teniposide is active against brain metastases of SCLC with a response rate of 36 % in a group of mostly pretreated patients.
INTERIM ANALYSIS OF A R4NDOMISED TRIAL COMPARING 3 WEEKLY VERSUS WEEKLY CHEMOTHERAPY (c%) IN PA’DENTS @‘IS) WlTH SMALL CELL LUNG CANCER (SCLC). D. W.Milesl, S.G.Spird, R.MRudd~, P.G.Harperl, C.M.Ash4, C.W.L.Trasks, Lhmeti, N.Gowel5, S.Barkerl, H.M.EarP, J.S.Tobiati, R.L.Souhami4. ‘Guy’s, 2RoyalBrompton, X~ndon Chest, Vniversity College and 3outhend Hospitals,London and Essex, England. 291 pts with SCLC with good prognostic features (all limited disease [LD] cases (181 pts) and extensive disease [ED] cases with ECOG status 0 or 1 & Alk phoscl.5~ normal (1lOpts)) have been randomised to receive && cisplatin &tmg/m* i.v. dl and etoposide (etop) 120mg/mz i.v. dl-3, alternating 3-week& with cyclophosphamide 600mg/m* i.v, doxorubicin (dox) 50mg/mz i.v. and vincristine 2mg i.v. dl to a total of 6 courses QI cisplatin 50mg/m* iv. dl and etop, 75 mg/mz i.v. d1+2 alternating M with ifosfamide 2g/m* i.v (with mesna) and dox 25mg/m* dl, to a total of 12 courses. Dose modifications were made according to defined haematological criteria. Postchemotherapy, pts with LD who acheived CR or PR were eligible for mediastinal radiation. Response rates:- 3-weekly overall response (OR) rate 80%, CR 33%. [LD, OR 848, CR 43%; ED, OR 73%, CR 17%]. yeeklv OR 83%, CR 30%. [LD, OR 842, CR 35%; ED, OR 828, CR 20%]. Median survival:- f &=43 weeks, weekly =45 weeks (p = n.s.) Toxicity:Neutropenia was the major dose limiting toxicity with weekly treatment. Other toxicities were not significantly different. Conclusions. Based on this interim analysis, there is no difference in response rates or survival between the two treatment ;;ifaeA Results of a quality of life questionaire are being
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PILOT STUDY OF MULTI-CYCLIC COMBINATION CHEMOTHERAPY (MCCCT) FOR EXTENSIVE SMALL CELL LUNG CANCER (SCLC) Kunihiko Kobayashi, Shuuji Kurane, Tetsuyuki Morikawa, Naotaka Nukariya, Mitsunori Hino, Hisanobu Nii tani Dept. of Respiratory Disease of Nippon Medical School, Tokyo, Japan Recently it was reported that there were AUC(ar,ea under the curve) dependent drugs and time dependent And we proved that SCLC ones in anti cancer drugs. cell lines needed only low threshold AUC of AUC dependent drugs such as CDDP, ADM, ACNU, and MMC to be killed. So to reduce toxicity and to make an advantane in SCLC chemotherauv. we olanned the MCCCT in which AUC dependent drugs-were g;ven at low doses at a time, but repeatedly given to get totally high AUC for a short time, and time dependent drug was administered as usual. That is to say, MCCCT was consisted of CPA ZOOmg/mZ, CDDP 30mg/m2, VCR 1 mg/body on day 1, ACNU 3Om /mZ, ADM 20mg/m2on day every ;,,;;;t,MMC 3mg/m2,VCR lmg$ body, and repeated
MIC CHEMOTHERAPYIN NSCLC MEN.
Sixteen extensive SCLC patients (Dts) (10 previously untreated CPU),-6 previously treated (PT)l with median age 69trange 44-76) and PS3 (range I-4:including six PS4 pts;4 PU and 2 PT) were.entered 15 pts without one early death due to to this study. disease progression were evaluable for response and toxicity. All the evaluable patients received’2 to 4 cycles (median 3). Response rate for PU and PTpts were 90% (9/10,95% confidence limits 60-98X) and 20% (l/5) respectively. Median WHOgrade of leukocytopenia and thrombocytopenia in the first cycle were Z(range O-3) and O(range 0) respectively. Other toxicities such as gastro-intestinal, liver, renal ones were mild. Median survival time was 27+ weeks for PU and 11 weeks for PT pts. It is thought that this MCCCT regimen was active for SCLC, and that it might be beneficial especially to poor risk patients. Further study is warranted.
NOT A PALLIATIVE
REGI-
P.Harnett, J.Taper, H.Gurney, P.Flynn, R.StuartHarris. Dept. of Medical Oncology, Westmead Hospital, Westmead, 2145, Australia, and Nepean Hospital, Penrith, Australia, 2750. Several recent studies report high (up to 60%) response rates in NSCLC using mitomycin C, ifosfamide and cisplatin. In a pilot study we treated patients with advanced NSfLC with mito C (6 mg/m I4, ifos amide/mesna (3 gm/m 1 and cisplatin (50-100 1 [MICI. mg/m Ten males, four females, median age 55 with Stage III-IV NSCLC were treated. Six patients had adenoCA, four large cell, and 4 squamous carcinoma. All patients were ECOG O-l. A mean of 2 cycles were administered. Tumour responses to therapy were CR=O, PR=2, SD=5, PD=7. Toxicity (N&V) was considerable. Although emesis on the day of treatment could be well controlled with antiemetics, protracted N&V Grade 11-111 occurred in the majority of patients despite the use of regular antiemetics, and 5 patients required readmission for control of emesis. Alopecia Grade 11-111 occurred in all patients. No other major toxicity was seen. The median survival all cases was 5 months. In our experience, the low response rates and toxicity of MIC make it unsuitable for use in the palliative treatment of NSCLC.
476
TNNIPGSIDB FOR BRAIN NBTASTASES OF WALL CELL LUNG CANCER, BORTC PRCTCCGL 08873 piater II. Postmus, Groningen; Nice van Bandwijk, Amsterdam; Andrea Ardirroni, Genus; Elisabeth Quoix, Strassbourg; Anne Kirkpatrick, Brussels and the EORTC LUNG CANCER COOPERATIVE GROUP. Brain metastases is the most devastating form of metastatic disease in SCLC occurring in over 50 % of the patients. Results of cranial radiotherapy are poor partly due to tumor progression outside the CNS, poor Performance Status and lack of machine time. In a previous study high-dose etoposide resulted in CT documented CR's and PR's, but this was associated with severe myelotoxicity and toxic death (Br J Cancer 1989, 5, 524). In this study the congener of eto side, teniposide, was given at a dose of 150 p4 mgfm on day 1, 3, 5 every 3 weeks to patients with brain metastases of SCLC, either at diagnosis (~11) or during treatment or follow-up. Response was evaluated by brain CT after 2, 6 and 12 cycles. Of 81 patients 72 were avaluable for response. Response was: 7 CR, 19 PR, 12 NC, 17 PD, 17 BD/TD (died within 42 days from start). Response rate 36 %. Of these patients survival was (medium (range)): CR 348 days PR 149 (70-393), NC 112 (44-2BO), PD 60 $S;;;~), . Toxicity was almost only hematologic with grade 4 myelotoxicity in 9 % of the courses. We conclude that teniposide is active against brain metastases of SCLC with a response rate of 36 % in a group of mostly pretreated patients.
INTERIM ANALYSIS OF A R4NDOMISED TRIAL COMPARING 3 WEEKLY VERSUS WEEKLY CHEMOTHERAPY (c%) IN PA’DENTS @‘IS) WlTH SMALL CELL LUNG CANCER (SCLC). D. W.Milesl, S.G.Spird, R.MRudd~, P.G.Harperl, C.M.Ash4, C.W.L.Trasks, Lhmeti, N.Gowel5, S.Barkerl, H.M.EarP, J.S.Tobiati, R.L.Souhami4. ‘Guy’s, 2RoyalBrompton, X~ndon Chest, Vniversity College and 3outhend Hospitals,London and Essex, England. 291 pts with SCLC with good prognostic features (all limited disease [LD] cases (181 pts) and extensive disease [ED] cases with ECOG status 0 or 1 & Alk phoscl.5~ normal (1lOpts)) have been randomised to receive && cisplatin &tmg/m* i.v. dl and etoposide (etop) 120mg/mz i.v. dl-3, alternating 3-week& with cyclophosphamide 600mg/m* i.v, doxorubicin (dox) 50mg/mz i.v. and vincristine 2mg i.v. dl to a total of 6 courses QI cisplatin 50mg/m* iv. dl and etop, 75 mg/mz i.v. d1+2 alternating M with ifosfamide 2g/m* i.v (with mesna) and dox 25mg/m* dl, to a total of 12 courses. Dose modifications were made according to defined haematological criteria. Postchemotherapy, pts with LD who acheived CR or PR were eligible for mediastinal radiation. Response rates:- 3-weekly overall response (OR) rate 80%, CR 33%. [LD, OR 848, CR 43%; ED, OR 73%, CR 17%]. yeeklv OR 83%, CR 30%. [LD, OR 842, CR 35%; ED, OR 828, CR 20%]. Median survival:- f &=43 weeks, weekly =45 weeks (p = n.s.) Toxicity:Neutropenia was the major dose limiting toxicity with weekly treatment. Other toxicities were not significantly different. Conclusions. Based on this interim analysis, there is no difference in response rates or survival between the two treatment ;;ifaeA Results of a quality of life questionaire are being
477
478
PILOT STUDY OF MULTI-CYCLIC COMBINATION CHEMOTHERAPY (MCCCT) FOR EXTENSIVE SMALL CELL LUNG CANCER (SCLC) Kunihiko Kobayashi, Shuuji Kurane, Tetsuyuki Morikawa, Naotaka Nukariya, Mitsunori Hino, Hisanobu Nii tani Dept. of Respiratory Disease of Nippon Medical School, Tokyo, Japan Recently it was reported that there were AUC(ar,ea under the curve) dependent drugs and time dependent And we proved that SCLC ones in anti cancer drugs. cell lines needed only low threshold AUC of AUC dependent drugs such as CDDP, ADM, ACNU, and MMC to be killed. So to reduce toxicity and to make an advantane in SCLC chemotherauv. we olanned the MCCCT in which AUC dependent drugs-were g;ven at low doses at a time, but repeatedly given to get totally high AUC for a short time, and time dependent drug was administered as usual. That is to say, MCCCT was consisted of CPA ZOOmg/mZ, CDDP 30mg/m2, VCR 1 mg/body on day 1, ACNU 3Om /mZ, ADM 20mg/m2on day every ;,,;;;t,MMC 3mg/m2,VCR lmg$ body, and repeated
MIC CHEMOTHERAPYIN NSCLC MEN.
Sixteen extensive SCLC patients (Dts) (10 previously untreated CPU),-6 previously treated (PT)l with median age 69trange 44-76) and PS3 (range I-4:including six PS4 pts;4 PU and 2 PT) were.entered 15 pts without one early death due to to this study. disease progression were evaluable for response and toxicity. All the evaluable patients received’2 to 4 cycles (median 3). Response rate for PU and PTpts were 90% (9/10,95% confidence limits 60-98X) and 20% (l/5) respectively. Median WHOgrade of leukocytopenia and thrombocytopenia in the first cycle were Z(range O-3) and O(range 0) respectively. Other toxicities such as gastro-intestinal, liver, renal ones were mild. Median survival time was 27+ weeks for PU and 11 weeks for PT pts. It is thought that this MCCCT regimen was active for SCLC, and that it might be beneficial especially to poor risk patients. Further study is warranted.
NOT A PALLIATIVE
REGI-
P.Harnett, J.Taper, H.Gurney, P.Flynn, R.StuartHarris. Dept. of Medical Oncology, Westmead Hospital, Westmead, 2145, Australia, and Nepean Hospital, Penrith, Australia, 2750. Several recent studies report high (up to 60%) response rates in NSCLC using mitomycin C, ifosfamide and cisplatin. In a pilot study we treated patients with advanced NSfLC with mito C (6 mg/m I4, ifos amide/mesna (3 gm/m 1 and cisplatin (50-100 1 [MICI. mg/m Ten males, four females, median age 55 with Stage III-IV NSCLC were treated. Six patients had adenoCA, four large cell, and 4 squamous carcinoma. All patients were ECOG O-l. A mean of 2 cycles were administered. Tumour responses to therapy were CR=O, PR=2, SD=5, PD=7. Toxicity (N&V) was considerable. Although emesis on the day of treatment could be well controlled with antiemetics, protracted N&V Grade 11-111 occurred in the majority of patients despite the use of regular antiemetics, and 5 patients required readmission for control of emesis. Alopecia Grade 11-111 occurred in all patients. No other major toxicity was seen. The median survival all cases was 5 months. In our experience, the low response rates and toxicity of MIC make it unsuitable for use in the palliative treatment of NSCLC.