7056 Background: The MPCRN phase III trial comparing the triplet PCG to the non-platinum doublet GV has been completed for pts with advanced NSCLC. Initially, a four-arm randomized trial was done and PCG and GV were associated with the best median survivals (Cancer 2002; 95:1279–85). GV was significantly less toxic than PCG, providing the rationale for extending the randomized comparison of PCG to GV as a phase III trial. Methods: The primary objective of this randomized phase III study was to compare survival of previously untreated pts with advanced NSCLC treated with PCG versus GV. PCG treatment consisted of P 200mg/m2 IV D1, C (AUC=5) IV D1, G 1000mg/m2 IV D1,8 q 21D. GV treatment was G 1000mg/m2 IV D1,8,15 q 28D and V 25mg/m2 IV D1,8,15 q 28D. Pts were re-evaluated q 2 cycles. Pts without evidence of progression or undue toxicity received a maximum of 6 cycles. Eligibility criteria included: stage IIIB/IV NSCLC, no prior chemotherapy, measurable disease, ECOG PS 0–2, adequate organ function, absence of brain metastases, and informed consent. Study was powered (0.80) to demonstrate an increase in expected 1-year survival from 30% with GV to 45% for PCG, requiring a total of 174 pts on each arm. P-values reported are two sided. Results: 349 pts were enrolled. Baseline pt characteristics were similar in the two groups. Objective response rates were similar for both regimens (PCG 25%; GV 26%). There was less grade 3/4 neutropenia, thrombocytopenia, anemia, alopecia, nausea/vomiting, myalgia/arthralgia and neuropathy (grade 2/3/4) with GV. One-year progression-free survival (PFS) and survival for PCG versus GV were 12% versus 15% (p=NS), and 39% versus 43% ((p=NS), respectively. Conclusions: In the first-line treatment of advanced NSCLC, PCG and GV are equivalent in terms of PFS and survival. Doublet non-platinum therapy with GV is associated with much less toxicity. Further study of GV in early stage NSCLC is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb

7151 Background: We have previously shown that weekly docetaxel (D) and weekly docetaxel/gemcitabine (D/G) are active well tolerated regimens for advanced NSCLC patients who are elderly or with poor PS or with serious comorbidities. This ongoing phase III trial was designed to compare the survival of patients randomized to single agent weekly D vs. weekly D/G and will require a total of 346 pts to detect an improvement of 1-year survival from 25% to 40%. The objective of this analysis is to compare the safety/toxicity of the two regimens. Methods: Eligibility included: stage IIIB/IV NSCLC, previously untreated, age ≥ 65 years or with serious coexistant medical illness or PS=2; adequate organ function, informed consent. Patients received either weekly D 36mg/m2 IV Days 1, 8, 15 every 28 days for 6 courses or D 30mg/m2 IV/G 800mg/m2 IV Days 1, 8, 15 every 28 days for 6 courses. Results: 214 patients have been enrolled in this ongoing trial. The clinical characteristics of patients, including serious comorbidities, in both treatment arms are similar (PS=2 in 33 pts and 29 pts, respectively). The incidence of several grade 3/4 toxicites was lower with D vs. D/G: neutropenia 5% vs. 16%; thrombocytopenia 0% vs. 8%; fatigue 13% vs. 17%; diarrhea 6% vs 10%. Hospitalizations (4% vs 17%) and treatment-related deaths (1% vs. 3%) were also less common with D vs. DG. The relative dose intensity was 90% (D) and 80% (D/V). There is no difference in toxicities in comparing PS 2 with PS 0, 1. Conclusions: The interim safety results of this trial show both therapies to be relatively well tolerated in this elderly patient population many with serious cormobidities and PS 2. This study continues with anticipated completion in 6–12 months. No significant financial relationships to disclose.

4018 Background: Optimal treatment for patients (pts) with localized esophageal cancer is unclear. In various reported trials, results with concurrent chemotherapy/RT have been comparable to results with treatment programs containing surgical resection. We previously demonstrated the efficacy of preoperative concurrent paclitaxel/carboplatin/5FU/RT in a large phase II trial (41% 3-yr PFS). In this trial, we attempt to further define the role of surgical resection by randomizing pts to resection vs completion of full dose RT, following the same preop therapy. Methods: Eligibility: untreated esophageal/GE junction squamous or adenocarcinoma; clinical stage I-III; surgical candidate; ECOG PS 0–2; adequate organ function; informed consent. All pts received paclitaxel 200mg/m2 IV and carboplatin AUC 6.0 IV, days 1 & 22; 5-FU 225mg/m2/day, 24-h continuous infusion, days 1–42; radiation therapy 45 Gy (1.8 Gy single daily fractions). After completion of preop treatment, pts were randomized to either surgical resection (4–6 weeks after preop therapy) or continued RT (total dose 64.8 Gy) plus 1 additional course of paclitaxel/carboplatin. Overall survival and PFS were the major endpoints. Results: Between 10/99 and 10/04, 194 pts were treated: median age 60 years; male/female 81%/19%; adenocarcinoma 72%; distal or GE junction location 84%; clinical stage I vs II/III 9%/91%. Following chemotherapy/RT, 89 pts (46%) agreed to randomization, and 57 pts proceeded with the treatment to which they randomized. When all patients are considered, resected pts (N=91) and full dose RT pts (N=50) had similar median PFS (20 vs 15 mo; p=.92), OS (27 vs 24 mo; p=.74), and 3-yr survival (35% vs 31%). Comparisons were similar in the subset of randomized pts. 4 pts (2%) had treatment-related death during induction; 3 pts (3%) had postop death. Conclusions: Attempts to randomize pts to resection vs full dose RT were largely unsuccessful. However, in large parallel groups of pts, these treatments produced similar PFS and OS, suggesting resection may not be a required component of combined modality treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb

7085 Background: Targeting VEGF has proven to be an effective tx strategy in many solid tumors including non-small cell lung cancer. VEGF expression in SCLC provides rationale for studying B in addition to chemoradiotherapy. Methods: The endpoints of this multicenter community-based study were to assess the safety, response rate (RR), and progression-free survival (PFS) of I/C/RT followed by B in patients (pts) with LS-SCLC. Tx included: C AUC = 5 IV D1, I 50mg/m2 IV D1,8 Q 21D x 4 cycles, and RT 1.8 Gy daily to a total of 61.2 Gy, beginning with the 3rd cycle. 3rd and 4th cycles were 28D each. Pts were restaged after 4 cycles. If no progressive disease (PD) pts received B 10 mg/kg IV Q 14D x 10 doses. Eligibility included: measurable disease, ECOG PS 0–1, informed consent, and no new brain metastases or bleeding. Results: Fifty-seven pts were enrolled from 8/03 to 10/04. Forty-five pts (79%) and 41 pts (72%) received planned tx with I/C/RT and B, respectively. The range of follow-up is 14–28 months. Baseline features: median age 65 years (42–80); male/female, 37%/63%; ECOG PS 0,1: 26%/74%. Grade (G) 3/4 non-hematologic toxicity: diarrhea (9%), DVT (4%), vomiting (11%), and fatigue (9%). G3/4 hematologic toxicity: neutropenia (37%), anemia (5%), and thrombocytopenia (13%). Only 9% of pts experienced G3/4 toxicity during B tx (1 pt each: DVT, hypokalemia, depression, pain, and colon perforation). There were 2 tx-related deaths (both from respiratory failure; 1 and 2 doses of B had been administered). Complete/partial responses were observed in 15 pts (26%)/31 pts (54%), respectively, for an overall RR of 80% (95% CI 70%-90%). Four pts had stable disease, and 5% had PD (4 pts were unevaluable.) 1- and 2-year PFS rates were 63% and 54%, respectively. 1- and 2- year overall survival (OS) rates were 71% and 29%, respectively. Median OS was 15 months. Conclusions: The safety, RR, and 1- and 2-year survival results of I/C/RT followed by B compare favorably with standard tx for LS-SCLC; and B may improve PFS. Assessing the role of B as maintenance tx in improving OS in this setting will require randomized trials. [Table: see text]

BACKGROUND: Patients with advanced non–small-cell lung cancer (NSCLC) and poor performance status (PS) are often excluded from trials. Gefitinib is a safe oral agent that may benefit these patients. PATIENTS AND METHODS: Seventy-two patients with poor PS and advanced NSCLC were enrolled onto this study of gefitinib 250 mg per day given orally until disease progression, with evaluation at 8 weeks. Eligible patients had no previous chemotherapy, an Eastern Cooperative Oncology Group PS of 2/3, and stage IIIB/IV NSCLC. Quality of life (QOL) and symptom response (SR) scores were calculated using the Functional Assessment of Cancer–Lung questionnaire. Patient characteristics included a median age of 75 years; PS of 2/3; and bronchoalveolar (n = 3), adenocarcinoma (n = 29), squamous cell (n = 21), large-cell (n = 11), and unspecified histology (n = 6). Mean treatment duration was 4 months (range, 3 days to 18 months), and median duration of follow-up was 12 months. Grade 3/4 toxicities included rash and diarrhea. RESULTS: Among 70 patients assessed for response, there were 3 partial responses (4%), 32 patients with stable disease (46%), and 18 with progressive disease (26%). Median progression-free survival (PFS) and overall survival (OS) were 3.7 months and 6.3 months, respectively. Six-month and 1-year PFS and OS rates were 35% and 21% and 50% and 24%, respectively. Eighty-two percent and 48% of patients reported improvements or no change in QOL and SR, respectively. CONCLUSION: Gefitinib demonstrates modest efficacy and is well tolerated as initial therapy in advanced NSCLC for patients with poor PS.

7086 Background: Gefitinib has single agent activity and excellent tolerability in patients (pts) with refractory non-small cell lung cancer (NSCLC) and may be of benefit to previously untreated poor performance status (PS) pts. Methods: The objectives were to evaluate the feasibility/toxicity, response rate, and symptom response (SR) of gefitinib in a total of 60 poor PS untreated pts. Eligible pts had no prior systemic therapy; ECOG PS 2, 3; stage IV or IIIB NSCLC; adequate organ function. Gefitinib 250 mg/day was given orally until disease progression, with initial evaluation at 8 weeks. Symptoms were evaluated at baseline and SR weekly using the Lung Cancer Subscale (LCS) of the FACT-L. Results: Twenty-five pts of the required 60 pts have enrolled to date (male/female 17/8); median age 64 (range 58–84); ECOG PS 2/3 20/5; stage IIIB/IV 7/18; bronchioalveolar/adenocarcinoma/squamous/large cell/or other 2/8/8/6/1. The median treatment duration was 3 months (range 1–7) and duration of follow-up 1.2 months (range 0.5–6 months). Grade 3/4 toxicities included: rash (1/10), diarrhea (0/0), elevated liver function test (0/0), dry skin/pruritis (0/0), and stomatitis (0/0). Eighteen pts are now evaluable for response. No partial responses have been seen. Eleven pts (61%) had stable disease and 8 of these 11 pts remain on study. Seven pts (39%) had progressive disease. Six of the 11 pts with stable disease had improved SR. Of the 25 pts enrolled, 8 have expired. Conclusions: Gefitinib is safe, well-tolerated and useful for symptom improvement as first-line therapy for some pts with poor PS. Further follow-up and additional evaluable pts will be provided. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca

Purpose: To assess the efficacy and toxicity of first-line single-agent rituximab, followed by re-treatment with rituximab at 6-month intervals, in previously untreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients and Methods: Forty-four previously untreated patients with CLL/SLL received rituximab 375 mg/m2 weekly for 4 consecutive weeks. All patients were required to have one or more indications for treatment. Patients with objective response or stable disease continued to receive identical 4-week rituximab courses at 6-month intervals, for a total of four courses. Results: The objective response rate after the first course of rituximab was 51% (4% complete responses). Twenty-eight patients received one or more additional courses of rituximab. At present, the overall response rate is 58%, with 9% complete responses. After a median follow-up of 20 months, the median progression-free survival (PFS) time was 18.6 months, and the 1- and 2-year PFS rates were 62% and 49%, respectively. Treatment was well tolerated, with only two episodes of grade 3 to 4 infusion-related toxicity. No cumulative toxicity or opportunistic infections occurred. Conclusion: Single-agent rituximab, used at a standard dose and schedule, is active in the first-line treatment of patients with CLL/SLL, producing substantially higher response rates than previously reported in relapsed or refractory patients (51% v 13%, respectively). Re-treatment with rituximab at 6-month intervals is well tolerated. The PFS time of 18.6 months in patients with CLL/SLL seems shorter than the 36- to 40-month median PFSs previously reported with first-line plus maintenance rituximab in patients with follicular lymphoma. Additional follow-up is required to fully assess the impact of this treatment strategy.

PURPOSE:To evaluate the efficacy and toxicity of the novel chemotherapy combination that includes gemcitabine, carboplatin, and paclitaxel in the treatment of patients with carcinoma of unknown primary site.PATIENTS AND METHODS:One hundred twenty patients were treated with the following regimen, administered every 21 days for a planned four courses: gemcitabine 1,000 mg/m(2) intravenously (i.v.) on days 1 and 8, carboplatin at an estimated area under the concentration-time curve of 5 mg min/mL i.v. on day 1, and paclitaxel 200 mg/m(2) i.v. on day 1. After four courses, stable and responding patients were given weekly paclitaxel 70 mg/m(2) i.v. for 6 weeks for three 8-week courses. All patients had relatively poor prognostic features. Sixty-three patients had well-differentiated adenocarcinoma, 56 patients had poorly differentiated carcinoma, and 104 patients had performance status of 0 or 1.RESULTS:Twenty-eight (25%) of 113 assessable patients (95% confidence interval, 22% to 30%) had major objective responses to treatment. Response rates were similar in the two major histologic types. Response rate did not seem to be improved by continued therapy with weekly paclitaxel. The median progression-free survival time was 6 months. Median survival for the entire group was 9 months, and the actuarial survival at 1 and 2 years was 42% and 23%, respectively.CONCLUSION:Combination chemotherapy with gemcitabine, carboplatin, and paclitaxel followed by weekly paclitaxel is an active and tolerable treatment for patients with carcinoma of unknown primary site. The survival seen in this poor-prognosis group of patients in this multicenter community-based trial is notable and similar to other taxane-based regimens for these patients. Study of additional combinations or sequences of newer drugs, as well as the exploration of targeted biologic agents for patients with an identified target in their tumors, is warranted.

PURPOSEThe purpose of this study was to evaluate the feasibility, toxicity, and efficacy of a novel combined-modality treatment for patients with locally advanced squamous carcinoma of the head and neck. PATIENTS AND METHODSIn this multicenter, community-based phase II study, 123 previously untreated patients with locally advanced squamous carcinoma of the head and neck received 6 weeks of induction chemotherapy followed by concurrent high-dose radiation therapy and weekly chemotherapy. Induction chemotherapy included paclitaxel (200 mg/m2, 1-hour i.v. infusion) on days 1 and 22, carboplatin (AUC 6.0 i.v.) on days 1 and 22, and 5-fluorouracil (225 mg/m2 per day, 24-hour continuous i.v. infusion) on days 1–43. After 1 week without therapy, radiation therapy, 1.8 Gy/day, 5 days weekly, to a total dose of 68.4 Gy, was administered to the primary site and the bilateral cervical lymph nodes. During radiation therapy, patients also received six weekly doses of paclitaxel (50 mg/m2, 1-hour i.v. infusion) and carboplatin (AUC 1.0 i.v). After completion of therapy, patients were restaged with computed tomographic and endoscopic examination; patients in complete remission were followed up without further treatment. RESULTSOne hundred twenty-three patients (74% with stage IV disease) entered this trial, and 111 patients (90%) completed the entire treatment course. Seventy of 116 evaluable patients (60%; 95% CI, 51%-69%) had a clinical complete response to treatment. After a median follow-up of 24 months, the 2-and 3-year actuarial survivals were 66% and 51%, respectively. Local toxicity was moderately severe during combined-modality therapy; however, xerostomia has been the only frequent chronic toxicity of this program. CONCLUSIONSThis novel combined-modality treatment program, containing paclitaxel and avoiding the use of cisplatin, is feasible, is highly active, and can be administered with acceptable toxicity in a community-based setting. Aggressive nutritional support should be considered in patients receiving this regimen, to improve acute palliation and to maximize the delivery of combined-modality therapy. Further evaluation of this treatment program is warranted. Incorporation of various novel biologic agents, particularly the epidermal growth factor receptor antagonists, may further improve efficacy.

PURPOSE:To evaluate the efficacy and toxicity of docetaxel administered weekly to elderly or poor-performance status patients with advanced breast cancer.PATIENTS AND METHODS:Forty-one patients with advanced breast cancer who were either over the age of 65 or considered to be poor candidates for combination chemotherapy received docetaxel 36 mg/m2 weekly for 6 consecutive weeks, followed by 2 weeks without treatment. The median age of patients in this trial was 74 years, and 73% of patients had one or more visceral sites of metastases. Seventy-five percent of patients received weekly docetaxel as first-line treatment for metastatic breast cancer, and the other 25% received it as second-line treatment. Thirty-six patients were assessable for efficacy, and all patients were assessed for toxicity.RESULTS:A total of 448 doses of weekly docetaxel were administered to 41 patients. Thirteen patients (36%) had objective responses to treatment, and an additional 13 patients (36%) had stable disease or minor response. Median time to progression for responding and stable patients was 7 months (range, 3 to 27 months). Median survival for the entire group was 13 months, with 1- and 2-year actuarial survival rates of 61% and 29%, respectively. Severe neutropenia occurred in only 0.4% of courses, and no other hematologic toxicity was observed. Grade 3/4 fatigue was the most common toxicity, occurring in 20% of patients.CONCLUSION:Weekly docetaxel therapy is active and well tolerated by elderly and/or poor-performance status patients with advanced breast cancer. This treatment can be administered with minimal myelosuppression. Weekly docetaxel provides an additional option for treatment in this difficult subgroup of patients with metastatic breast cancer. Well-tolerated combination regimens containing weekly docetaxel merit evaluation for this patient population.

Weekly administration of docetaxel was found to reduce myelosuppression and other nonhematologic toxicities when compared with administration every 3 weeks. In the current Phase II trial, the authors evaluated the feasibility, toxicity, and efficacy of weekly docetaxel in the treatment of elderly patients with newly diagnosed advanced nonsmall cell lung carcinoma.

Twenty-nine patients with advanced pancreatic adenocarcinoma were treated with merbarone, utilizing a daily intravenous schedule for 5 days. Only two partial responses of short duration were observed. The major toxicities were renal, with an increase in creatinine or proteinuria in 17 patients, and mild to moderate nausea and vomiting seen in 22 patients. Merbarone in this dose and schedule has minimal activity in pancreatic cancer.

Seventeen patients with malignant ovarian germ cell tumors were treated with vinblastine, actinomycin D, bleomycin and cisplatin containing combinations. Many of these patients were heavily pretreated. Thirteen patients had objectively measurable disease and ten (77%) had an objective response (CR or PR). Four patients had nonmeasurable disease or were treated in an adjuvant setting and all remain without evidence of disease. Extensive disease and poor performance status were poor prognostic factors. Induction portions of these treatment programs which contained cisplatin appeared most effective. Maintenance portions without cisplatin appeared less effective.