Intratumoral Therapy I: Association of Immunotherapy with Permanent Long Term Cure of Metastatic Cancer

Abstract

We have demonstrated in a randomized prospective study the superiority of intratumoral (intralesional) dinitrochlorobenzene (DNCB) compared to intratumoral (intralesional) bacillus Calmette-Guerin (BCG) in the treatment of progressive metastatic melanoma. The metastatic melanoma was in the form of satellitosis and/or in-transit metastases. We now demonstrate the ability of intralesional DNCB to permanently cure a selected group of patients with the same clinical criteria, and describe their clinical characteristics and treatment regimens. The described cured patients were followed for their remaining lifetimes, for up to 30 years, after being immunotherapeutically rendered free of metastatic cancer. They were each female, between the ages of 51 and 56 when intratumoral treatments were begun. Treatment was for progressive cutaneous and subcutaneous metastatic disease in the leg in two cases and for rapidly spreading scalp and forehead metastases in another. In each case the disease was not surgically controllable. Treatments were continued for 6 to 26 months. Subsequently the patients survived tumor free for either 18 years, dying at age 83; or for 24 years, dying at age 89; or for 30 years, dying at age 97. There has been a significant interest in recent years in immunotherapy for advanced cancer. The absence of systemic toxicity in the cured patients reported herein provides a basis for consideration of combining intratumoral treatments with current effective but systemically more toxic immunotherapeutic approaches to some metastatic cancers. Intratumoral treatments may be particularly applicable in cases of uncontrollable melanoma with cutaneous metastases, without evidence of distant spread, as in the current report.