Early recovery of aggressive cytotoxic cells and improved immune resurgence with post-transplant immunotherapy for multiple myeloma.

A phase I/II trial evaluated early administration and dose escalation of interleukin (IL)-2 with granulocyte macrophage colony stimulating factor (GM-CSF) post-transplant. Following melphalan (200 mg/m(2)) and an autologous transplant, IL-2 was initiated (day 0) and continued for 4 weeks. GM-CSF (250 mcg/m(2)/day) began on day 5. Fifteen of 19 patients completed therapy. No treatment-related deaths occurred. IL-2 (1 x 10(6) IU/m(2)/day) was not tolerated in two of six patients due to > or =grade 3 fatigue/diarrhea (n=1) or supraventricular tachycardia (n=1). The maximum tolerated dose of IL-2 was 6 x 10(5) IU/m(2)/day; this dose was well tolerated by 11 of 13 patients. Neutrophil and platelet engraftment occurred on day 13 (median; range 10-17 days) and day 13 (median; range 0-74 days), respectively. When compared to control patients, there was a marked increase in the number of CD3+ T cells (P=0.005), CD4+ T cells (P=0.01), CD8+ T cells (P=0.001) and CD4+CD25+Treg cells (P=0.015) post-transplant. Cytotoxicity directed against myeloma cells was markedly increased when compared to control patients (P=0.017). This unique trial design using early administration of IL-2 with GM-CSF during the period of lymphodepletion, demonstrated a marked increase in the number and function of early cytotoxic effector T cells, without suppression of engraftment.

A brief historical review of the development of chemotherapy for the treatment of advanced non-small cell lung cancer: why we should look beyond platinum.

We are approaching the end of the fifth decade and the most productive period in the development of chemotherapy for the treatment of advanced non-small cell lung cancer. We began this decade by establishing cisplatin-based combination chemotherapy regimens of the 1980s as effective at improving survival for patients with advanced disease. The observed improvement in survival from these trials appears to be primarily attributed to cisplatin. Furthermore, this decade, unlike the prior, has identified an abundance of novel active agents for the treatment of this disease. Vinorelbine, gemcitabine, docetaxel, paclitaxel, and irinotecan are all new chemotherapeutic agents which have shown promising activity in this disease. In contrast to the cisplatin-based chemotherapy trials of the 1980s, these newer chemotherapeutic agents when given in combination with cisplatin add to the survival outcomes for these patients. With these survival advances has come a focus on chemotherapy-induced adverse events, lung cancer symptom management, and overall quality of life. The results of the cisplatin combination trials will be discussed.

New oral chemotherapeutic agents for lung cancer.

Anticancer treatment has recently shifted to include a broad range of antineoplastic therapies. Old agents are continuously being re-evaluated, and new mechanisms of treatment are rapidly being explored and developed. At the same time, the patient's perceived quality of life, adverse effects of therapy, time demands, and healthcare costs have become paramount in the treatment process. Lung cancer is the most common cause of cancer death in the USA, and because many of the patients are older or debilitated, these issues become all the more important. The oral administration of anticancer therapy offers both quality-of-life and healthcare cost advantages. Oral forms of 3 new cytotoxic agents and 2 novel oral therapies are discussed. Vinorelbine, a vinca alkaloid, has well documented activity in non-small cell lung cancer. Myelosuppression is dose limiting; neurotoxicity is rare. Satraplatin (JM-216), an oral platinum derivative, shows activity in lung cancer with a favourable adverse effect profile, with no neurotoxicity or nephrotoxicity. The oral topoisomerase I inhibitor topotecan may be ideal for obtaining long term low plasma drug concentrations, which appears to maximise efficacy. LGD-1069 is a retinoid X receptor agonist that modulates cell proliferation, and BAY-129566, a matrix metalloproteinase inhibitor, appears to interrupt both the processes of angiogenesis and metastasis. LGD-1069 and BAY-129566 are nontraditional anticancer agents which may be used in conjunction with chemotherapy, other modalities, or in prevention. These 5 agents will be discussed with particular reference to recent developments in the treatment of lung cancer.