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Latest Article

Melanoma Vaccines: What We Know So Far

Vaccines are a promising but still experimental treatment for melanoma.They are intended to stimulate immune responses against melanomaand by so doing, increase resistance against and slow the progressionof this cancer. Key requirements for vaccines to be effectiveare that they contain antigens that can stimulate tumor-protective immuneresponses and that some of these antigens are present on thetumor to be treated. Unfortunately, these antigens are still not known.To circumvent this problem, polyvalent vaccines can be constructedcontaining a broad array of melanoma-associated antigens. Severalstrategies are available to construct such polyvalent vaccines; each hasadvantages and disadvantages. Clinical trials have shown that vaccinesare safe to use and have much less toxicity than current therapy formelanoma. Vaccines can stimulate both antibody and T-cell responsesagainst melanoma, with the type of response induced, its frequency,and its magnitude depending on the vaccine and the adjuvant agentused. A growing body of evidence suggests that vaccines can be clinicallyeffective. This evidence includes correlations between vaccineinducedantibody or T-cell responses and improved clinical outcome,clearance of melanoma markers from the circulation, improved survivalcompared to historical controls, and most convincingly, two randomizedtrials in which the recurrence-free survival of vaccine-treatedpatients was significantly longer than that of control groups.

Latest Article

Multiple Myeloma in the Elderly: When to Treat, When to Go to Transplant

Until recently, standard treatment of multiple myeloma (MM) in elderly patients who were not candidates for autologous stem cell transplantation was with the combination of melphalan plus prednisone (MP). Novel agents (thalidomide, lenalidomide, bortezomib) are dramatically changing frontline therapy of MM. Randomized studies have shown the superiority of adding one novel agent to MP, either thalidomide (MPT) or bortezomib (MPV). The combination of lenalidomide with low doses of dexamethasone is another attractive alternative. Recent results show that maintenance therapy with low-dose lenalidomide may prolong progression-free survival. The objective of these improved treatment regimens should be to achieve complete response, as in younger patients. However, toxicity is a significant concern, and doses of thalidomide and of myelotoxic agents should be reduced in patients who are older than 75 years or who have poor performance status. Weekly bortezomib appears to induce severe peripheral neuropathy less frequently than the same agent administered twice weekly. Autologous stem cell transplantation is feasible in selected fit patients over 65 years of age, and its results are improved by the addition of novel agents before and after high-dose therapy. However, considering the progress in non-intensive therapy, autologous transplantation should not currently be offered to elderly patients outside of a clinical trial.

Latest Article

Gemcitabine/Paclitaxel as First-Line Treatment of Advanced Breast Cancer

Gemcitabine (Gemzar) and paclitaxel exhibit good activity and goodsafety profiles when used alone and together in the treatment of advancedbreast cancer. In a phase II trial, 45 patients with metastaticbreast cancer received gemcitabine at 1,200 mg/m2 on days 1 and 8 andpaclitaxel at 175 mg/m2 on day 1 every 21 days. Twenty-seven patients(60.0%) had prior adjuvant therapy. Objective response was observedin 30 patients (objective response rate 66.7%, 95% confidence interval[CI] = 52%–71%), including complete response in 10 (22.2%) and partialresponse in 20 (44.4%). Median duration of response was 18 months(95% CI = 11–26.7 months), median time to tumor progression for theentire population was 11 months (95% CI = 7.1–18.7 months), medianoverall survival was 19 months (95% CI = 17.3–21.7 months), and the1-year survival rate was 69%. Treatment was well tolerated, with grade3/4 toxicities being infrequent. Grade 3/4 leukopenia, neutropenia, andthrombocytopenia were each observed in six patients (13.3%). No patientwas discontinued from the study due to hematologic ornonhematologic toxicity. Thus, the gemcitabine/paclitaxel combinationshows promising activity and tolerability when used as first-line treatmentin advanced disease. The combination recently has been shownto be superior to paclitaxel alone as first-line treatment in anthracyclinepretreatedadvanced disease according to interim results of a phase IIItrial and it should be further evaluated in comparative trials in breastcancer.