Bevacizumab in combination with carboplatin and paclitaxel improved overall response and time to progression in patients with advanced or recurrent non-small-cell lung cancer. Patients with nonsquamous cell histology appear to be a subpopulation with improved outcome and acceptable safety risks.

DLI results in complete remissions in a high percentage of patients with relapsed chronic-phase CML. Complete remissions are observed less frequently in patients with advanced CML and acute leukemia. GVHD and pancytopenia occur commonly; GVHD is highly correlated with response.

While the improvement in the primary end point TTP did not achieve statistical significance, this study suggests that sipuleucel-T may provide a survival advantage to asymptomatic HRPC patients. Supportive studies are underway.

ONYX-015 is an adenovirus with the E1B 55-kDa gene deleted, engineered to selectively replicate in and lyse p53-deficient cancer cells while sparing normal cells. Although ONYX-015 and chemotherapy have demonstrated anti-tumoral activity in patients with recurrent head and neck cancer, disease recurs rapidly with either therapy alone. We undertook a phase II trial of a combination of intratumoral ONYX-015 injection with cisplatin and 5-fluorouracil in patients with recurrent squamous cell cancer of the head and neck. There were substantial objective responses, including a high proportion of complete responses. By 6 months, none of the responding tumors had progressed, whereas all non-injected tumors treated with chemotherapy alone had progressed. The toxic effects that occurred were acceptable. Tumor biopsies obtained after treatment showed tumor-selective viral replication and necrosis induction.

The recommended dose for disease-directed studies of OSI-774 administered orally on a daily, continuous, uninterrupted schedule is 150 mg/d. OSI-774 was well tolerated, and several patients with epidermoid malignancies demonstrated either antitumor activity or relatively long periods of stable disease. The precise contribution of OSI-774 to these effects is not known.

BACKGROUND: Sipuleucel-T is an investigational active cellular immunotherapy product designed to stimulate an immune response against prostate cancer. The safety and efficacy of sipuleucel-T was evaluated in 2 identically designed, randomized, double-blind, placebo-controlled trials (D9901 and D9902A) conducted in men with advanced prostate cancer. METHODS: A total of 225 patients were randomized in D9901 or D9902A to sipuleucel-T (n ¼ 147) or placebo (n ¼ 78), given as 3 intravenous infusions approximately 2 weeks apart. Patients were followed for survival until death or a prespecified cutoff of 36 months after randomization. RESULTS: In the integrated analysis of D9901 and D9902A, patients randomized to sipuleucel-T demonstrated a 33% reduction in the risk of death (hazard ratio, 1.50; 95% confidence interval, 1.10-2.05; P ¼ .011; log-rank). The treatment effect remained strong after performing adjustments for imbalances in baseline prognostic factors, poststudy treatment chemotherapy use, and non-prostate cancer-related deaths. Additional support for the activity of sipuleucel-T is provided by the correlation between a measure of the product's potency, CD54 up-regulation, and overall survival. The most common adverse events associated with treatment were chills, pyrexia, headache, asthenia, dyspnea, vomiting, and tremor. These events were primarily grade 1 and 2, with durations of 1 to 2 days. CONCLUSIONS: The integrated results of D9901 and D9902A demonstrate a survival benefit for patients treated with sipuleucel-T compared with those treated with placebo. The generally modest toxicity profile, coupled with the survival benefit, suggests a favorable risk-benefit ratio for sipuleucel-T in patients with advanced prostate cancer. Cancer 2009;115:3670-9.

The 26% response rate, with durability in both injected and uninjected lesions including visceral sites, together with the survival rates, are evidence of systemic effectiveness. This effectiveness, combined with a limited toxicity profile, warrants additional evaluation of JS1/34.5-/47-/GM-CSF in metastatic melanoma. A US Food and Drug Administration-approved phase III investigation is underway.

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