S284 Abstracts Not Presented/Combined Modality Therapy: NSCLC

of NT with a non-platinum-based regimen consisting of gemcitabine (G) and vinorelbine (V). Patients and

Methods: Pts with proven NSCLC were staged with CT, PET, and medi- astinoscopy. G (1 ,000mg/m2) and V (25mg/ms) were given on days 1, 8, 22, and 29. Restaging with CT and PET was done between days 43 and 56, and surgery was done between days 57 and 70. To date, 30 pts have been enrolled.

Results: Two pts received only Dl of GV. One missed follow-up appoint- ments, and the other developed drug-induced hepatitis. They were removed from analysis. Six patients have not yet completed restaging. Among the 22 evaluable patients, 14 had pStage IB, 1 p.S IIA, 3 pS IIB, 3 pS IIIA, and 1 pS 1118. Using RECIST criteria based on CT, 15 had stable disease (SD), 4 had partial remission (PR), 3 had progressive disease (PD), and none had com- plete remission (CR). Twenty pts went to surgery, and resection was complete in 18. Three pts have died, 1 is lost to F/U, and 18 are alive. Survival ranges from l-29 months. None of the 20 pts that had surgery achieved a pathological CR. NO case of GC-related pneumonitis has occurred.

Conclusion: GC can be safely given as NT to resectable pts with NSCLC. Evaluation of tumor specimens for markers of proliferation, apoptosis, progno- sis, and prediction of treatment response will be presented.

q Patterns of failure after effective local therapy: results of a phase l/II clinical trial for inoperable NSCLC using pulsed paclitaxel radiosensitization

Yuhchvau Chen, Kishan Pandya, Therese Smudzin. University of Rochester Medical Center, Rochester, USA

Background: NSCLC remains the most lethal cancer due to difficulty in control- ling both local and distant disease. We recently reported the clinical outcome of a phase l/II clinical trial for inoperable NSCLC using pulsed low-dose paclitaxel radiosensitization strategy. The in-field primary tumor control was superior and durable. The survival outcome was comparable to large randomized trials using full-dose chemoradiation (Clin Cancer Res 9:2003). We report first sites of fail- ure in this cohort of patients to understand the pattern of distant failure. We will show examples of CT and PET images to demonstrate durable primary tumor control and sites of distant failures.

Methods: A phase l/II clinical trial was conducted between 1998 and 2002 for patients with inoperable stages l/II and stage III NSCLC and one mesothe- lioma. Low-dose paclitaxel was delivered on Monday, Wednesday, and Friday mornings with 15mg/m’ to 20mg/ms. Radiotherapy was 60-65 Gy to gross disease and 45-58 Gy for potential microscopic disease. RT was delayed after chemotherapy to allow for a minimum of 5 hours of ceil cycle arrest in G2/M. All patients were followed with imaging studies and physical examinations 4- 6 weeks post-therapy and q 3 months thereafter. Sites of first failure were ana- lyzed based on imaging studies. Mesothelioma was excluded from this analysis.

Results: of 41 patients enrolled in the protocol, 33 completed treatments. Eight patients did not complete protocol treatments due to allergic reaction (3), distant disease spread during treatment (3) and intercurrent disease (2). Me- dian follow-up for all patients enrolled was 10 months. There were 2 in-field failures out of 41. Twenty-six had out-of-field failures. For these 26 patients, 34.6% (n=9) failed in brain, 30.8.% (n=8) failed in the thorax at sites distant from primary tumors, 15.3% (n=4) failed in soft t issue/abdomen, 11.5% (n=3) failed in bone, and 7.7% (n=2) failed of pericardial effusion,

Conclusions: While pulsed low-dose paclitaxel radiosensitization resulted in superior and durable primary tumor control, failures distant from primary tumor through hematogenous spread remains a problem. The two most common first sites of distant failure were brain and intrathoracic distant sites. The information provides insight to future strategic management of NSCLC.

q Preoperative chemotherapy in early stage NSCLC: Parallel randomized Phase II trials

Frank C. Detterbeck’, Mark A. Socinski’, M. Patricia Rivera’, Martin J. Edelmanz, Joshua R. Sonett3, Harry Raftopoulo$, Richard J. GraIlas. ’ Multidisciplinary Thoracic Oncology Program, University of North Carolina at Chapel Hill, Chapel Hi//, NC, USA; 2 University of Maryland Greenbaum Cancer Center, Baltimore, MD, USA; 3 Columbia Presbyterian Hospital, New York, NY USA

Preoperative chemotherapy in early stage NSCLC may improve survival. Down- staging and pathologic complete response (pCR) have been shown to be major prognostic factors with this approach. We developed a series of phase II stud- ies to identify a preoperative chemotherapy regimen in stage I or II NSCLC that resulted in a high pCR rate, with survival, response, toxicity and QoL as sec- ondary endpoints. In trial 1 patients are randomized to receive Gemcitabine (G) and Paclitaxel (P) or G and Carboplatin (Cb). In trial 2 patients are randomized to receive G and Cisplatin (Cis) or G/Cb. Three cycles of chemotherapy are given every 21 days at doses of: G - 1000 mg/m” dl,8; P - 200 mg/m’ dl (3h); Cb - AUC 5.5 dl; Cis - 80 mg/ma dl. To date 21 patients have been enrolled

on trial 1 and 20 on trial 2, with preliminary data available in 18 and 11. Clinical stage distribution in trial 1 was 28% cl, 72% cll, and in trial 2, 18% cl and 82% cll. No pCR has been seen so far. Grade 3 or 4 toxicity on cycle 1, 2, and 3 was experienced by 29%, 36%, and 21% of patients in trial 1, and in 50%, 40%, and 30% of patients in trial 2, respectively. Response and survival data will be presented for all available patients at the time of the meeting.

cl 44 Chemotherapy paclitaxel, carboplatin and etoposide with concurrent radiotherapy in the treatment of locoregionally advanced non small cell lung cancer (NSCLC)

Jana Kaplanova’, Marcela Tomiskova’ , Lenka Babickova’ , Olga Kubova’ , lvana Palkova’, Pave1 Slampa’, Jana Skrickova’. ’ University Hospital, Brno Bohunice, &no, Czech Republic; ’ Masaryk Memorial Cancer lnstifufe, Brno, Czech Republic

Concurrent chemo and radiotherapy is considered as an effective approach for locally advanced NSCLC. The simultaneous use of cytostatics and irradiation should improve the efficacy and enable radical surgical resection of primary locally advanced lung tumors. The chemotherapy consisted of paclitaxel, car- boplatin and etoposide. The drugs were applied weekly (6 times) or biweekly (3 times) with concurrent radiotherapy of primary tumor and mediastinal struc- tures. The dosages of cytostatics for the whole therapy were: paclitaxel 180- 360 mglms, carboplatin 600 mg/m”, etoposide 300 mglm’. The radiotherapy was given in daily fractions of 2 Gy up to 60 Gy for six weeks. The indications were: histologically or cytologically proved locoregionally advanced NSCLC stages Ill A/B, no prior treatment, adequate hematological and biochemical pa- rameters, PS O-2. Forty-three patients (pts), 38 males and 5 females with a mean age 59 years were treated. The stage Ill A was diagnosed in 29 and stage Ill B in 11 pts, unspecified stage Ill in 3 pts. The achieved dose intensity of applied chemotherapy and radiotherapy was satisfactory when 37(86%) pts received 80% or more out of planned dose. Dose of drugs and radiotherapy reaching 50-79% out of planned dose was delivered to 5(12%) pts, 1 patient re- ceived less than 49% out of planned dose. The hematological toxic profile was favorable with anemia G3/4 in 2(5%), granulocytopenia G 3/4 in 17(40%) pts. Febrile neutropenia had occurred in 2(5%) pts. Esophagitis G3 has developed in 8(19%) pts. Pulmonary toxicity occurred in 2(5%) patients. The tumor was radicallz resected in 13(30%) pts and nonradical surgery was in 1 pt. Thera- peutic response (CR+PR) was achieved in 25 (58%) pts, CR in 6 (14%) pts and PR in 19(44%) pts. Verification of CR was done in 5 pts. Nineteen (44%) pts reached l-year survival, 4(9%) pts reached P-years’ survival.

El 45 Neoadjuvant Chemotherapy of Nonsmall Cell Lung Cancer (NSCLC)-Stage IIIA By Regimen PaclitaxeVCarboplatin

Vftizslav Kolek’, lvona Grygarkovaa, Jiri Klein3, Marian Hajduch4, Vladimir Krals. ’ Pa/a&y University, Olomouc, Olomouc, Czech Republic; ‘University Hospital, Olomouc, Olomouc, Czech Republic; 3 Depf. of Surgery University Hosp. Olomouc, Olomouc, Czech Republic; 4 Laboratory of Experimental Medicine, Olomouc, Olomuc, Czech Republic; s Dept. of Surgery Olomouc, Olomouc, Czech Republic

Present study evaluates 27 patients with marginally resectable NSCLC (stage IIIA, PS O-l) treated by paclitaxel (P) 200 mg/m’ - day 1 and carboplatin (CB- DCA) AUC6 - day 1, in 21 day regimen given as neoadjuvant therapy. Restag- ing was performed after 3 cycles and surgery was indicated when possible. In inoperable patients radiotherapy was applied. Tolerability of treatment, re- sectability and survival were evaluated. Mean age of patients was 55.7 years (20 males,7 females). Histological types were squamous cancer (17) adeno- carcinoma (7)Jarge cell (I), bronchioloalveolar (1) and non-differentiated can- cer (1). Most frequent side effects of grade Ill were: myalgia (5.3%) neuropenia (4.0%) anorexia (2.7%) leucopenia (1.3%) and weakness (1.3%). Neutrope- nia of grade IV appeared in 2.7% of cycles. Out-patient system of treatment was well tolerated. Downstaging was achieved in 13 pts (48.2%) tumour dimin- ished in 6 pts (22.2%) and progression was observed in 8 pts (29.6%). Surgery was performed in 18 pts (66.7%), complete resection was possible in 16 pts (59.3%). Pneumonectomy was performed in 6 pts, sleeve pneumonectomy in 2 pts, bilobectomy in 3 pts and lobectomy in 7 pts. Mean survival after resection is 36.2 months (median 32 m), mean survival in group without resection is 13.3 m (median 13 m). In group after resection 15 patients still live, only 2 patients live in group treated with radiotherapy. Regimen P with CBDCA is an effective and well tolerated neoadjuvant treatment in patients with NSCLC. Number of severe side effects is low and out-patient system of care before surgery is comfortable for patients.