O-154 Impact of maintaining Hb with epoetin alfa on time toprogression (TTP), overall survival (OS), quality of life (QOL) and transfusion reduction in limited disease SCLC patients

Oral Sessions / Smafl ceil lung cancer by etpposido 240mglm ~ orally for 2 days) every 3 weeks. Pat]ants were desely monitored with mid-cycle full blood count Thoracic radiotherapy and PCI wore considered for patients with limited disease Results: 273 pat]ants (129 for ACE and 144 for PE) patients wore randomiTed Pre-tTeetment characterist]os were well balanced for stage, performance status. and age Pat]ants e0¢porienced similar alopecia, lethargy, anorexia, mucosltis and anemia but more sept]cemia on the ACE arm The PE arm had more grade 2 and 3 nausea. Grade 3 and 4 eeub'openia were observed in 97% patients on the ACE arm vs. 61% on the PE arm (p < 0.005). Thrombooytopenia 57% vs. 51% and anemia 29% vs. 22%. 79% grade 3 and 4 infections were observed on ACE arm and 30% on the PE arm (p < 0.005). Hosp~talisat]on required for severe neulzopenia and infections was less with PE. compared to ACE (350 days for iv ant]blot]os compared to 118.5 days for ACE. p < 0 005) Response rates for ACE and PE were 7,5% and 90% respectively 224 (8.9%) pat]ents have died Median survival was 9 7 (ACE) and 107 (PE) months One-year survival rates for the extensive stage group were 17% for the ACE arm and 13% for the PE arm and 2 years survival rates were 0% and 2% respectively One-year survival rates for the limited stage group were 44% for the ACE arm and 52% for the PE arm and 2 years survival rates were 19% and 17% respectwoly. Conclusions: ACE chemotherapy in SCLC pat]onts is assooated with higher risk of neutToponlc sepsis than plat]num based PE chemotherapy wlth no significant difference on the response rate and the survival time.

~lmpact of maintaining Hb with epcetln alfa on Ume to progression (TIP), overall survival (OS), quality of life (QOL) and tTansfuslon reduction In limited dlseese SCLC patfants G. Goss ~. R. Fold 2. A. BezJal~. G. Perry I . B. Melosky ~. C. Smith 4. M. Snoe~. R Plants G. C Lau G ~Ottawa Regtonal Cancer Centre, Ottawa, Canada,

~Pnncess Margaret Hospital, Toronto, Canada: ~Brt~sh Columt~a Cancer Agency, Vancouver, Canada, 4Tom Baker Cancer Centre, Ca~gary, Canada, Cookndge Hospttal, Leeds, U ~ eOrtho B/otech, Dtws/on of Janssen~Ortho Inc., Toronto, Canada Background: Limited disease SCLC patients are known to respond well to concurrent chemotherapy and thoracic irradiation. The importance of radiation therapy has been demonslzated with data suggesting concurrent and accelerated radiat]on treatments improve survival The goal of this study was to evaluate if maintaining Pigher Hb levels (target 14 16 g/dL) with epoet]n alfa could enhance the effec0veness of concurrent platinum-based chemoraclation therapy by improving local tumour control, and extending "I-FP and OS Methods: Patients scheduled to receive concurrent platinum (~>60mg/m2/q/cle clsplat]n or ~>5mg/mL AUC earboplatin) plus etoposlde (~>80mg/m2/day for 3 days) chemotherapy and radiation therapy (,5000cGyi2,5 fract]ons or 6000cGy/30 fractions) were randomized in a doubleblind study to either QW 40.0001U opoetin alfa or placebo. Study drug was to continue through to completion of PCI. if PCI was given. Complete tumour staging was requred at baseline and end of study, and tumour response was followed over time. Protocol endpolnts included TTP. OS. Hb response, trans~slon reduction. QoL and safety assessments. Results: LD SCLC patients were enrolled in the trial over 2 years from pa~cipating centTes in Canada. UK. Belgium. Span and Italy Baseline demographic vanables (age. gender, race. smoking history, pro-study weight loss) from 104 enrolled patients were equally balanced between tTeetment groups The mean baseline Hb level in both groups was 13,sg,'dL Placebo pat]ants expenenced a drop of Hb to a mean of 10g/dL (maintained through transfusional support), whereas epoetin alfa pat]ants maintained a higher Hb in the range of 13 13 5g/dL The number of pat]ants transfused throughout the study decreased by -70% in the opeetin alfa arm (51.9% placebo vs 15.4% epcetin alfa). Although patients exgenonced a drop in LASA QOL (Energy. Daily Act]vtt]es. Overall QOL) in both treatment groups, the drop was greater for placebo patients compared to apoet]n alfa patients (trend to slgnifieanee). Grade 3 and 4 adverse events were evenly disthbuted between t]'eatment arms. with except]on to vascular thrombotio events (VTE.s). The higher "vr]]-- incidence in the epoet]n alfa arm (31% eqoot]n alfa vs 4% placebo) resulted in early tnal terminat]on Higher Hb levels at time of study drug init]ation (>13~'dL) were identified as tTending to significance as a risk factor for VTE occurrence (p 0 09,56) At the time of analysis, there was no signlfieant difference in T I P (p 0 8291) and OS (p 0 2260) between epeatin alfa and placebo groups Overall response rates were similar between treatment groups (92 9% epoetin alfa vs 8.0 6% placebo), in patients where RR was confirmed 6 weeks postchemotherapy Follow-up for long-term survival cont]nues unt]l all tTial patients have surpassed 16 months post~'andomlzation. Conclusions: Epoetin alfa was OffK~OOUS in mainteirlng Hb levels and significantly decreasing b'ansfusions dunng concurrent platinum based chemoradiation therapy. The increased incidence of V3Es observed correlates to nigher Hb levels than are recommended in the management of oncology

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patients. No dif~rence was observed in T i P and OS between epoet]n alfa and placebo patients

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Randomized phase III trial of carboplatln (Cb) or clsplaUn (P) In combination with etoposlde (E) In elderly or poor-risk patients with extensive dlsesse small cell lung cancer (ED-SCLC): Report of a Japan Clinical Oncology Group Trlal (JCOG9702)

H. Kunitoh I , H OkamotJ, K Watanabe 2, H Kunlkane 2, A Yokoyama 2, S. Kudob 2, N. Ishizuka2, H. F~kuda 2, T. Tamura 2, N. SaijJ. ~Nat/onal Cancer

Center Hospttal, Tokyo, Japan, 2Japan C/in/ca/Onco/ogy Group, Japan Background: Platinum and etoposide combinat]on chemotherapy (Cx) is widely accepted as standard for SCLC Supst]tutJon of P with Cb or dose reduct]on/split dose(s) of P is employed for unfit pat]ants (pts) We conducted a phase III trial companng ECb with spilt-dosed EP in elderly or poor~isk pts with SCLC. Methods: Pts wlth pathologically documented ED SCLC or limited disease 0-D) with malignant effusion were eligible if. age ~>70 and performance status (PS) 0-2. or ago < 70 and PS 3. Pts must have had adequate organ function and no pnor therapy Pts were randomized, with minimization method balanong institution. PS (0-1 vs. 2-3) and ago (/>70 vs. <70). to receive either ECb: Cb (AUC ,5) div day 1 and E 80mg/m 2 (:iv days 1 3. or EP: P 25 mg/m 2 div days 1 3 and E 80mg/m 2 (:iv days 1 3 Both were given in a 21-day oycle for 4 courses Pdmary endpolnt was overall survival (OS) Assuming 110 eligible pts in each arm. the study had 80% power to detect 0 67 hazard rat]o for ECb to EP in OS at two-sided alpha of 0 05 Palliation scores for 8. symptoms (cough. pain. anoresia, shor'mess of breath, malaise, nausea, bowel disturbance and sleeplessness) were taken before and 9 weeks after inltiat]on of the Cx Results: From Aug/g8 and Feb/04. 220 pts were randomized, with 219 ovaluablo. Baseline charactonst]os wore well balanced; median age 74 years (92% of pts />70 years). >5% weight loss: 29%. M/F: 86/12%. PS 0-1/2-3: 74/26%. Four courses of Cx were completed in 62% of ECb and 65% of EP. Grade 3-4 thrombocytopenia was more frequent in ECb. but other major tosiclt]es, including neutropenia. GI symptoms and renalJhepat]c ones. wore similar between the arms and generally manageable (Table). Toxic deaths occurred in 2 pts in ECb and 1 pt in EP. Palliation scores were analyzable for all 21 g pts At 9 weeks, total symptom scores were improved in ,58% of pts As of SepJ04 monitoring, median OS and progression-free survival (PFS) for the 219 pts wore 10 2m and 4 9m. respect]vely Data will be available for the final analysis in Feb J0`5 Table: Major toxlot]es (%) Toxicity Gr3 4 Gn3-4 Gn3-4 Gr3 4 Gr.3-4 ~>Gr. 2 ~>Gr 2 ~>Gr. 2 ~>Gr. 2

ECb (n neutTopania anemia thrembocytoponia infection hypoxemia nausea diarrhea creat]rlne AST/ALT

95 30 55 f 7 24 9 2 11

110)

EP (n

109)

88. 24 16 6 3 26 4 4 13

Conclusions: Both combinat]on Cx wore well tolerated in unfit pts with advanced SCLC, and survival data appear pmmisthg Final condosions are to be obtained after the final analysis and should be available at the meet]ng

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RandomlzKI, phase III trial comparing Irlnotecan/clsplatln with etoposlds/clspletln In patients w l ~ previously untreated, extensive-stage, small-call lung cancer (SCLC)

C. Lanoor~. N. Hanna 2. L. Einhorn ~. A. Sandier 4. R. Arisen ~. P. Ellis B. M Byrne 7. M Green D. M Morrison 9. P Bunn 1° 1Fox Chase Cancer Center,

Phtladelph/a, Pennsylvania, USA: 2trial/aria Untverstty, lnd/anapot/s, tN, USA: 3Indiana Cancer Paw/ion, Indianapolis, IN, USA, 4 Vanderb~it University Medical Center, Nashvtlle, TN, USA: ~Northem ln~ana Cancer Research Consort/um, South Bend, IN, USA: eJurawns~ Cancer Centre, Harm/ton, Ontario, Canada: 7Sir Charles Ga/rdner Hospital, Nedands, Western Australta, Austral~a: SUn/varsity ot Melbourne, Patfrvtlle, Vtctona, Austral/a: gPltzer Oncology, New York, IVY, USA: ~°Un/versity of Colorado, Denver, CO, USA Background: Etoposide/clsplatin

(LP) has been the standard b'eatmont for estenslv~stage SCLC. A phase III study shewed improved overall survival (OS) for patients rec.eivlng innotocarv'clsplat]n (IP) vs. EP (Noda K ot al. N Engl J Mad. 2002;346:85-91). The current thai was designed to confirrn these results