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Background Gatipotuzumab is a humanized monoclonal antibody recognizing the carbohydrate-induced epitope of the tumor-associated mucin-1 (TA-MUC1). This study aimed to evaluate the efficacy and safety of switch maintenance therapy with gatipotuzumab in patients with TA-MUC1-positive recurrent ovarian, fallopian tube, or primary high-grade serous peritoneal cancer. Patients and methods In this double-blind, randomized, placebo-controlled, phase II trial, patients with at least stable disease (SD) following chemotherapy were randomized 2:1 to receive intravenous gatipotuzumab (500 mg followed by 1700 mg 1 week later) or placebo every 3 weeks until tumor progression or unacceptable toxicity occurred. Stratification factors were the number of prior chemotherapy lines (2 versus 3-5), response versus SD after the most recent chemotherapy, and progression-free survival (PFS), Highlights • Evaluation of the efficacy and safety of a switch maintenance therapy with gatipotuzumab. • Patients with TA-MUC1-positive recurrent ovarian, fallopian tube, or primary high-grade serous peritoneal cancer evaluated. • Gatipotuzumab is a humanized monoclonal antibody recognizing the carbohydrate-induced tumor-associated epitope mucin-1. • Gatipotuzumab was well tolerated, with mild to moderate infusion-related reactions. • Gatipotuzumab switch maintenance therapy does not improve outcome in TA-MUC1-positive ovarian cancer patients.

Background Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). Patients and methods An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). Results Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873–1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835–1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698–1.33; P = 0.8336]. The safety profiles were comparable between arms. Conclusions There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.

Summary. Limited data are available concerning treatment and outcome of primary lymphoma of the breast (PLB), especially after CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine, prednisone) chemotherapy. We retrospectively reviewed 20 consecutive cases of localized PLB seen at our institution over a 20 year period. All PLB were of B-cell origin: treatment was CHOP or a CHOP-like regimen in all patients. Sixteen of the 20 patients achieved complete remission (CR) and two achieved partial remission (. 75% tumour regression). Two patients had progressive disease on therapy. With a median follow-up of 54 months, six patients relapsed after 8‐66 months. Two of the relapses involved the central nervous system (CNS) (isolated in one case, associated with other sites of relapse in the other). The two patients who achieved partial remission also had progression in the CNS, 4 and 8 months after the end of CHOP chemotherapy. All four patients have died as a result of their disease 3, 6, 10 and 13 months after CNS relapse. Of the 16 centroblastic diffuse large B-cell lymphoma (DLCL), three had CNS disease at relapse. We also observed three (15%) controlateral breast relapses. Thirteen of the initial 20 patients are alive in CR, six patients have died as a result of their lymphoma and one of unrelated disease. In conclusion, we observed a high incidence of CNS relapse in this group of localized extranodal lymphoma, strongly suggesting that CNS prophylaxis should be associated with systemic chemotherapy in localized PLB.

Background: AGI004 is a controlled-release transdermal patch preparation of mecamylamine. We conducted a randomised placebo-controlled phase II study of two dose levels of AGI004 in chemotherapy-induced diarrhoea (CID). Methods: Adult patients receiving chemotherapy who had experienced diarrhoea (NCI grade 1–2) during previous cycles of chemotherapy were eligible. In all, 64 patients were randomised to receive AGI004 4 mg then 8 mg per 24 h transdermal patch or placebo for two sequential cycles of chemotherapy. Patients' severity of diarrhoea was physician-assessed using NCI grade of diarrhoea and patient-assessed using information recorded in daily diaries of bowel movements. Results: Overall AGI004 doubled the odds of a response to treatment on the first day of chemotherapy based on physician assessment of NCI grade of diarrhoea compared with placebo (odds ratio=2.0, 90% confidence interval: 0.9–4.5) and there was a trend to improved response rates for AGI004 for the full treatment cycle although these results were not statistically significant. There was also evidence of significantly improved response rates based on patient assessment of diarrhoea both overall (P=0.05) and at the 8-mg dose level (P=0.02) compared with placebo. Conclusion: AGI004 demonstrated effectiveness in reducing chemotherapy-associated diarrhoea, with results suggesting response across multiple measurements of diarrhoea. Treatment was well tolerated with no drug-related adverse events. Further evaluation of this agent in the management of CID is warranted.

Topotecan has recently shown activity in small cell lung cancer (SCLC) patients. The aim of the present phase II study was to assess the antitumor activity and toxicity of the combination of topotecan plus etoposide in chemotherapynaive patients with advanced SCLC on an outpatient basis.From December 1998 to February 2001 24 previously untreated patients with histologically proven advanced (stage IIIB and IV) SCLC received topotecan 1.2 mg/m(2), days 1-5, followed by etoposide 100 mg/m(2), days 8-10, every 3 weeks, up to 6 cycles (less if progressive disease).Twenty-two patients were males and 2 females. Their median age was 54 years (range 37-67 years). World Health Organization (WHO) performance status (PS) was 0-1 in 12 patients and 2 in 12. AJCC stage IIIB was found in 6 patients and IV in 18.76 cycles (median 3.5 cycles) were given with no toxic deaths. Grade 4 toxicity was registered in 10 (13%) cycles for neutropenia, 4 (5%) cycles for anaemia, 1 (1.3%) cycle for thrombocytopenia and 1 (1.3%) cycle for diarrhea. Activity: among 23 evaluable patients, 8 had an objective response to chemotherapy (response rate - RR- 34.7%, 95% confidence interval -CI- 14-55%) with 4 (17.4%) complete remissions (CRs) and 4 (17.4%) partial remissions (PRs). Survival: with a median follow-up of 8 months (range 1.5-25 months), one-year actuarial survival was 48% (95% CI 28-69%) and median survival was 47.8 weeks.Although the combination of topotecan and etoposide proved easy to administer on an outpatient basis with moderate and manageable toxicity, it showed only moderate activity as first-line chemotherapy in advanced SCLC.

To determine the efficacy, toxicity and survival of concurrent therapy with vinorelbine and a platinum compound with radiotherapy (RT), followed by consolidation chemotherapy with the same drugs, for locally advanced non small cell lung cancer (NSCLC).Fifty-seven patients with stage III NSCLC were included in this phase II study: median age 56 years (range 44-71), males / females 49/8, ECOG performance status (PS) 1/2=27/30, stage IIIA/ IIIB 11/46, squamous cell carcinoma 44, adenocarcinoma 7, adenoid cystic carcinoma 1 and large cell carcinoma 5. Treatment consisted of 2 cycles of chemotherapy with vinorelbine and cisplatin or carboplatin, given concurrently with RT, followed by 2-4 more cycles of consolidation chemotherapy with the same drugs. Twenty-two patients received amifostine for radio- and chemoprotection.Grade 3 or 4 toxicities were neutropenia and esophagitis in 19% of the patients each, and gastrointestinal toxicity in 17% of the patients. Of the 55 patients evaluable for response, 23.64% achieved complete response (CR) and 40% partial response (PR) (overall response rate 63.64%). Progression-free survival curves showed 1- and 2-year values of 42% and 21%, respectively, and median time to progression 10.5 months. The 1- and 2- year disease-specific survival was 58% and 29%, and the median overall survival 15 months.Preliminary analysis indicates that concurrent vinorelbine and a platinum compound with RT followed by consolidation chemotherapy with the same drugs for advanced stage III NSCLC is well tolerated, has considerable activity and positive impact on survival.

Among mechanisms potentially involved in resistance to alkylating agents and anthracyclines, the glutathione system has been extensively studied in vitro. We analyzed by immunohistochemistry the relation between glutathione s-transferase pi (GST-pi) expression in tumor cells and outcome in 69 cases of diffuse large B-cell NHL (DLBCL). GST-pi expression was considered as low when50% of tumor cells were stained and high when/=50% tumor cells were stained. Median follow-up was 58 months. GST-pi expression was correlated with the probability of achieving complete remission (CR). Patients with high GST-pi expression had a worse 5-year freedom from progression (FFP). High GST-pi expression was associated with a trend for lower survival. In the group of patients with International Prognostic Index (IPI) 0-1, low GST-pi expression was associated with a CR rate of 88%, a 5-year FFP of 76+/-20% and a 5-year survival of 78+/-16% compared to 36, 14+/-16 and 40+/-32%, respectively, in patients with a high GST-pi expression (P=0.002, P10(-5) and P=0.01, respectively). No correlation was found between GST-pi expression and lactico deshydrogenase serum level, age, Ann Arbor stage, performance status, and IPI index. Both GST-pi expression and the IPI index correlated with FFP. After incorporating IPI and GST-pi expression in a multivariate analysis for FFP, GST-p expression remained the only prognostic factor (P=0.003). Our findings suggest that GST-pi expression had strong prognostic significance in DLBCL, which appears to be independent of other prognostic parameters in those disorders.

Limited data are available concerning treatment and outcome of primary lymphoma of the breast (PLB), especially after CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine, prednisone) chemotherapy. We retrospectively reviewed 20 consecutive cases of localized PLB seen at our institution over a 20 year period. All PLB were of B-cell origin: treatment was CHOP or a CHOP-like regimen in all patients. Sixteen of the 20 patients achieved complete remission (CR) and two achieved partial remission (75% tumour regression). Two patients had progressive disease on therapy. With a median follow-up of 54 months, six patients relapsed after 8-66 months. Two of the relapses involved the central nervous system (CNS) (isolated in one case, associated with other sites of relapse in the other). The two patients who achieved partial remission also had progression in the CNS, 4 and 8 months after the end of CHOP chemotherapy. All four patients have died as a result of their disease 3, 6, 10 and 13 months after CNS relapse. Of the 16 centroblastic diffuse large B-cell lymphoma (DLCL), three had CNS disease at relapse. We also observed three (15%) controlateral breast relapses. Thirteen of the initial 20 patients are alive in CR, six patients have died as a result of their lymphoma and one of unrelated disease. In conclusion, we observed a high incidence of CNS relapse in this group of localized extranodal lymphoma, strongly suggesting that CNS prophylaxis should be associated with systemic chemotherapy in localized PLB.

8029 Background: The Raf/MEK/ERK signaling pathway is necessary for oncogenic function, and in NSCLC pts constitutive activation of this pathway has been correlated with BRAF/KRAS gene mutations. MEK1/2 inhibition block the Raf/MEK/ERK pathway since these kinases lie downstream of Ras, and ERK1/2 are the only known substrates of MEK1/2. Here we evaluate the efficacy and safety of oral AZD6244 - a potent, selective, ATP uncompetitive inhibitor of MEK1/2 - vs pemetrexed (PEM), which is currently approved and widely used for second/third-line treatment, in pts with advanced NSCLC. Methods: Pts who have previously received one or two chemotherapy regimens (prior surgery and/or localized radiation allowed) were randomized 1:1 to oral AZD6244 (100 mg BID) or iv infusion of PEM (500 mg/m2 over 10 min q3w). Pts in the PEM arm also received corticosteroid premedication and vitamin supplementation. The primary objective of this Phase II exploratory study was to evaluate the efficacy of AZD6244 vs PEM as second- or ...