The following is a summary of data from the American Association for Cancer Research, National Cancer Institute and European Organization for Research and Treatment of Cancer conference, which ended Friday in San Francisco. (See also pages 8 and 9.)

• AEterna Zentaris Inc., of Quebec City, reported positive results of tests on three AEZS-112 (formerly ZEN-012) follow-up, multitargeted, cytotoxic candidates. AEZS-112 is a multitargeted cytotoxic compound currently in a Phase I trial for solid tumors and lymphoma. Results showed that all three follow-up candidates were equal to or more efficient in exerting cytotoxic activity in tumor cell lines and inhibiting tubulin polymerization than AEZS-112, and induction of cell cycle arrest and apoptosis was slightly improved. In vitro plasma and liver microsomal stability of the follow-up candidates were comparable to AEZS-112, demonstrating suitability for in vivo efficacy studies.

• Allos Therapeutics Inc., of Westminster, Colo., presented results of a Phase I dose-ranging study for PDX (pralatrexate), an antifolate, when given with vitamin B12 and folic acid supplementation. A total of 22 patients with relapsed or refractory non-small-cell lung cancer (NSCLC) were treated at doses of 150 mg/m2 to 325 mg/m2, and the maximum tolerated dose was determined to be 270 mg/m2, which is twice that observed in a previous Phase I study of PDX administered without vitamins. Clinically significant radiologic responses were observed. Based on the results the company plans to initiate a randomized Phase II study of PDX in patients with NSCLC.

• Celator Pharmaceuticals Inc., of Princeton, N.J., reported positive results from preclinical studies to evaluate the optimal ratio of irinotecan and cisplatin to deliver synergistic benefit against a range of tumor cell lines in vitro. The study further worked to develop an effective formulation to maintain the optimal ratio of the drugs in vivo. Specifically, combinations of irinotecan and cisplatin were applied to a panel of 20 human and murine tumor cell lines enriched with lung tumor carcinomas in vitro to identify the ratios most likely to deliver synergistic benefit. The combination exhibited strong drug ratio dependent synergy, Celator said.

• Cell Therapeutics Inc., of Seattle, disclosed new preclinical data from several drug candidates, showing potential progress toward identifying, early in development, specific tumor types with a higher likelihood of demonstrating response to anticancer compounds. Among the abstracts was one related to a new class of thienopyrimidine Src inhibitors that demonstrates potent growth suppression of imatinib resistant Ba/F3 cells harboring a wide range of BCR-ABL mutations, including the CML relevant T315I.

• Chemokine Therapeutics Corp., of Vancouver, British Columbia, reported preliminary results from its Phase I/II trial of CTCE-9908, which demonstrated that the drug is well tolerated with no dose-limiting toxicity observed up the maximum dose of 5 mg/kg/day. The main side effect at the top dose was moderate phlebitis. Results also showed that seven out of 20 cancer patients had stable disease after one month, and one patient with small-bowel carcinoma showed stable disease after six months of therapy. The company also presented preclinical results with CTCE-9908, a peptide analogue of the chemokine SDF-1, showing that it inhibited tumor cell migration and significantly reduced circulating tumor cells in the blood, resulting in a significant reduction in the number of animals with metastases. A third presentation demonstrated that CTCE-9908 treatment in combination with chemotherapy, either in an adjuvant or consolidation schedule, reduced the metastatic area by 40 percent to 50 percent in animal models.

• CuraGen Corp., of Branford, Conn., and TopoTarget A/S, of Copenhagen, Denmark, offered positive data from Phase II trials with intravenous belinostat in combination with carboplatin and paclitaxel for relapsed ovarian cancer, and from two Phase II studies sponsored by the National Cancer Institute with the I.V. drug as monotherapy for ovarian cancer. The companies also offered Phase I safety and dose-escalation trail results with oral belinostat.

• Semafore Pharmaceuticals Inc., of Indianapolis, presented data showing its PI3 kinase inhibitor SF1126 is active against tumor and tumor cells and synergizes with chemotherapy agents. In vitro data showed significant (p<0.001) synergistic growth inhibition of prostate cancer cells with combinations of docetaxel and SF1126, as well as synergistic growth inhibition of brain cancer cells with combinations of doxorubicin and SF1126. In addition, SF1126 and rapamycin showed excellent growth inhibition synergies across all prostate, renal and non-small-cell lung cancer cell lines. Simultaneous dosing of SF1126 with docetaxel in a prostate xenograft model exhibited slightly improved tumor response time vs. administering SF1126 prior to docetaxel administration. In the same xenograft model, using very large tumors, it was shown that SF1126 in combination with docetaxel gave significantly greater tumor regression than did docetaxel alone (p<0.05). SF1126 as a single agent showed significant tumor growth inhibition relative to the control group (73 percent inhibition, p<0.01) in that model as well.

• Sunesis Pharmaceuticals Inc., of South San Francisco, presented positive preliminary results from the first stage of its ongoing Phase II clinical trial of its lead product candidate, SNS-595, in platinum-resistant ovarian cancer patients. Administered as a single agent, SNS-595 demonstrated antitumor activity, with 88 percent (15 of 17) of evaluable patients achieving stable disease or better, including two partial responses. Based on those results, SNS-595 achieved the prespecified criterion of two or more responses for proceeding to stage 2 of the trial. Patients were treated once every three weeks by I.V. infusion for up to eight cycles. SNS-595 was generally well tolerated at the current dosing level among 19 patients with sufficient follow-up to yield safety data. Incidence of febrile neutropenia was 11 percent (two of 19) among those patients. In addition, 5 percent (one of 19) of patients experienced grade 3/4 nausea and 11 percent (two of 19) experienced grade 3/4 fatigue.

• Telik Inc., of Palo Alto, Calif., reported positive preclinical data from its program to develop small-molecule inhibitors of validated cancer targets including aurora kinases and VEGFR2. Telik said its scientists have identified a class of selective small-molecule inhibitors of aurora kinase A and B and VEGFR2. Treatment of human colorectal cancer cells with two of those inhibitors, A60 and EA19, prevented cell division, ultimately leading to cancer cell apoptosis. Those same compounds are potent inhibitors of VEGF-dependent human endothelial cell proliferation. Those agents demonstrated significant inhibition of tumor growth in a standard xenograft model of human colorectal cancer.