Adoptive immunotherapy of patients with metastatic renal cell cancer using lymphokine-activated killer cells, interleukin-2 and cyclophosphamide: long-term results

Abstract

Background: Initial results of adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) appeared to offer promise for treating renal cell cancer (RCC). However, lower response rates were seen in subsequent trials, and the long-term results of this treatment method have not been fully reported. In this study, we examine long-term results of adoptive immunotherapy using LAK cells, IL-2, and cyclophosphamide (LAK/IL-2/CPM therapy).

Methods: We administered 10 courses of therapy to 9 patients with advanced RCC. One patient had liver and para-aortic lymph node metastases; the others had only lung metastases. The clinical effects were initially evaluated 4 weeks after therapy and follow-up was continued for periods of 43 to 76 months.

Results: The 4-week evaluation revealed 3 complete responses (CR), 3 partial responses (PR), 1 minor response (MR), 1 patient with no change in disease status (NC), and 2 patients whose disease progressed (PD). One CR patient remained apparently free of disease for 43 months. After tumors recurred in the lung of another CR patient further disease progression was suppressed by IL-2 administration until the patient died from other causes at 46 months. The third CR patient showed tumor recurrence in the lung and was re-treated with the same LAK/CPM/IL-2 therapy. Lung tumors decreased in size (PR), but the patient died due to brain metastasis 2 months after the second round of treatment. The 2 initial PR patients, as well as the MR and NC patients, developed regrowth or new metastatic lesions within 2 to 15 months following therapy. The 2 PD patients died 2 and 9 months after therapy.

Conclusion: Long-term effects of LAK/IL-2/CPM therapy were not correlated with the maximal response observed 4 weeks after therapy. Although LAK/IL-2/CPM therapy appears suitable for use as induction therapy in RCC, our data suggest that long-term suppression will require surgical removal of remnant tumors or more intensive maintenance therapy.