P-778 A phase II trial of carboplatin and irinotecan as first-line therapy for extensive stage small cell lung cancer (ES-SCLC): Preliminary results

Posters/Smafl ceil lung cancer Results: Up to December 2004. 36 patients were assessable. The median follow-up time was 12,5 months A total of 209 infusions (mecian 6 per patient) were administered The actual dose intensity values were cisplatin 19.7mg/m2/week and innotecen 37.7mgtm2/week. Among the 16 limited disease (LD) patients, the oblect]ve response rate was 94.4% (17 patients). with 8 patients (44.4%) having a complete response (CR). Among the 20 extensive disease (ED) patients. 17 (85%) had a response and 1 (,5%) had a CR. The major grade 3/4 hematological tox]cit]es were neutrepenia (32.5% of cycles), anemia (5 8% of cycles), thmmbocytopenia (4 8% of cycles) Febrile neutmpenia was 4 8.% of cydes The predeminant grade 3/4 non~ematologicel tmdcitJea was ciarrhea (3 4% of cycles) ToxicitJes was not significantly different with concurrent administ~al~on of irinotecen and cisplatJn with raciotherapy. except grade 3/4 radiation eaephagitJs (28.% of patients) No treatment-related deaths were observed Data for survival will be reported Conclusions: Three-week schedule of irinotecen plus cisplatin is an effec~ve treatment for limited and extensive disease small call lung cancer, with acceptable toxicity. ~P~6~ Phase II ~ a l of Irlnotecan and clsplatln wRh concurrent radiotherapy In limited-disease small cell lung cancer J Kim. Y Moon. J Sohn Yonsei Cancer Center, Yonsei University Co/legs

or Mac~cine, Saoul, Soulh Korea Background: We performed a phase II tnal of innotecan and c~splatin with concurrent radiotherapy in limited
Phase I study of comblnetlon Irlnotecan and clsplatln and either twice dally ~oraclc ra¢lation (45Gy) or once dally thoradc radiotherapy (-fOGy) In patients with limited small cell lung carolnoma (SCLC): Early toxicity analysis of RTOG 0241

C. Lanoer ~. S. Swann ~. M. Wemer Waslk ~ . R. Lillenbaum 4. W. Curran s. A Sancller e. N Scidmore z. H Chcy ~. M Samuels fFox Chase Cancer

Center, Ph//adelpt#a, PA, USA: ~Rad/at/on Therapy Oncetogy Group, Philadelphia, PA, USA, 3Thomas Jefferson University HospitaJ, Plu/adelphia, PA, USA, Mr. S/nat Cancer Center, M/arm Beach, FL-# USA, Thomas Jefferson University Hospttal, Philadelphia, PA, USA, Vandert~it University Medical Center, Nashville, TN, USA, ZUniversity # Alabama, Birmingham, B/rrmngt~am, AL, USA/e Vandert,}/it School ct Medicine, Nasht~//e, TN, USA Background: Irincteosn in combination with cisplal~n has proven superior to etoposldd and cisplatin in extensive stage SCLC in one small phase III trial (Neda et al NEJM 1/2002). with a neady fourfold advantage in two-year survival (19 `5% vs `5 2%) Given this benefit, we sought to determine ifirinotecen could be sa~ly integrated with concurrent radial~on and cisplal~n in limited SCLC Methods: Eligibility stipulated t]'eatment~aive, limited stage SCLC. Zubred PS 0-1. FEV 1 /> 1 liter and adequate physiologic function. Enrollees received a fixed dose of cisplal~n 60 mg/m 2 q 3 wks x 4 and either BID RT to 4,5 Gy (Seq A [Arm 1]) or QD RT to 70 Gy (Seq B [Arm 2]) Irinotecen was given days 1 and 6 q 3 wks x 4 and escalated in sequential cohorts from 40mg/m ~ (level 1) to ,50 mg/m (level 2) to 60 m~'m 2 (level 3) Chemotherapy was given concurrently with RT during the 1s~ cycle in Sequence A. and during the 1st two o/c/as in Sequence B Acute DLT was defined as grade (gr) 4 esophagitJs, pneumonitis. or ciarrhea; gr 4 neub'openic fever; or any att]lbutable gr 5 fatal toxicity (~<90 days after RT). Results: As of 1/4/05.26 patients have been enrolled: 7 in Sequence. A level 1 ; 7 in Sequence A. level 2; 6 in Sequence B. level 1 ; and 4 to date in Sequence

S323

B. level 2. Median age is 64. range (49-79). Of 24 evaluable pts. only 9 (38%) are male 17 (71%) have Zubmd PSi) Level 1 Leva4 2 Saquaace A SequsrlCe B Seauenc,sA

S,~uanc,s B

Total

To]tel Pts T~C
7 7 0 E (2) 5(0)

8 8 0 4 (1) 4(1)

7 5 0 3 (0) 2(0)

4 1 0 1 (1) 1(1)

26 21 0 14 (4) 12(2)

Esophaomt]s Naus~]/vorrIit]n0

0 (0) 2 (0)

I (0) 2 (0)

I (0) 0 (0)

0 (0) 0 (0)

2 (0) 4 (0)

Dmarmea

3 (0)

2 (0)

0 (0)

1 (1)

6 (1)

To date. there has been no att~butable DLT (see table) 4 pts have axperienced gr 4 neLrlTobenia, inducing 2 with gr 3 febrile neutmpenia 2 pts. both in sequence B. have had gr 4 cardiovascular tmdcity There has been no acute gr ,5 toxicity, and no late grade 4 tmdcity 1 pt experienced late gr 3 pulmonary toxicity and another late gr 3 constitutional toxicity, including wt loss Conclusions: In limited SCLC. in combination with cisplatJn 60mg/m 2 every 3 wks x 4 and either BID RT (45Gy) or QD RT (70Gy). irlnotecan 40 mg/m 2 d 1 and 8. is safe and ~asible In addition, irinctecen at 50m~'m 2 days 1 and 8 q 3 wks x 4 is feasible in combination with cisplalJn and BID RT: results ~r sequence B level 2 (70 Gy total) are pencing Response. progression, and survival data remain immature ~8]A

phase II klal of carboplatin and Irlnotecan as flret-Ilne therapy for extenalve stage small cell lung cancer (ES-SCLC): Preliminary raSUltS

J Lasldn I B Shirley2. T Dobbs 3.J Bi 4. D Carbone ~.D Johnson ~. A Sander s. ~BntJsh Columt~a Cancer Agency, Vancouver, Canada:

2 Vander~/tqngram Cancer Center Affiliate Network, Nashville, USA, SBaptist Hospital of East Tennessee, Knoxwl/e, USA, St. Thomas Hospital Nashwl/e, USA. Vandett~it University Medical Center, Nash~lle, USA Background: The combination of irinotecan and cisplalJn has been shown to significantly improve the survival of palJents with extensive small call lung osncar (ES-SCLC) over a standard etoposide/cisplatin combiealJon in a thai conducted by the Japanese Clinical Oncology Group (Noda: NEJM 2002) Two phase III confirmatory trials are underway in North America CarboplalJn has bread-spectTum anti-tumour activity and is commonly used as a lass toxic alternative to clsplat]n. The safety and tolerabillty of this comb/nation has been demonstrated in phase I stucles (Okamoto; ASCO 2004). The primary oblectrve of tils study is to assess the efficacy of this comb/nation. Methods: This is a multi~,,enter study in patients Cots) ~ t h previously untreated ES SCLC. The chemotherapy is given on a 21 day schedule: innotecan 50mg/m 2 (days 1. 8) and cerbeplatin AUC ,5 (day 1): to a maximum of 6 cycles Results: As of Dec 21. 2004. 16 pts of a planned 54 were enrolled. Pt charactenstios were as follows: median age 62 yrs; male/female: 10/4. ECOG PS 0 (3); 1 (10); 2 (1). All pts were either current or former smokers. A median of 3.5 and a total of 49 o/des were delivered to 16 pts. 8 pts campleted ~>4 o/des. None of the 49 planned doses of carbpplatin were missed. 6 doses were reduced. Of the 89 planned doses of innotecan. 7 were missed (all day 8) and 16 required a dose reduot]on. The average doses delivered were 606 mg and g9 mg. of cerboplalJn and irinotecan, respectively Toxicity data is available on 14 pts The rate of grade 3 / 4 neutrepenia and thrombocytobenia was 7 (,50%) and 2 (14%). respecOvely There were no episodes of ~brile nsutTopenia Grade 3 (no grade 4) non-hematologic toxicitiea included: diarrhea 1 (7%): alopecia 1(7%): nausea 1 (7"%) ,5 pts stopped treatment eady: 1 (PD): 1 ineligible (limited disease): 1 death: 2 toxici'das (myelosuppression) Followup data is available on 12 pts (average 105 days of follow-up): 1 pt is currently receiving b-eatment and 3 pts have died. Of the 12 pts evaluable for response: CR 0; PR 7 (58%); SD 2 (17%); PD 2 (17%). Conclusions: While enrollment in this 1~al is ongoing these preliminary results demonstrate the tolerabll~ and encauraging efficacy of the combination of carboplat]n and innotecan in ES SCLC. [P-~]

Impact of anamla on outcomes of therapy In limited small cell lung cancer (L-SCLC): An analysis of studies performed by me National Cancer Institute of Canada Clinical Trials Group OMCIC CTG)

S Laurie 1,2 K Ding 2. M Whitehead 2. R Feld 2. N Murray 2. L Seymour~. E Shepherd 2. 1Ottawa Hospttal Reg/ona/Cancer Centre, Ottawa, Canada:

2National Cancer/nstttute of Canada Cl/mca/ Trials Group,/~ngston, Canada Background: Anemia dunng chemoradiat]on has been assooated with a poorer outcome in a vanety of turnour types, induding non SCLC. and