Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery.

The recent literature documents the growing interest in local intratumoral chemotherapy as well as systemic preoperative chemotherapy with evidence for improved outcomes using these therapeutic modalities. Nevertheless, with few exceptions, the conventional wisdom and standard of care for clinical and surgical oncology remains surgery followed by radiation and/or systemic chemotherapy, as deemed appropriate based on clinical findings. This, in spite of the fact that the toxicity of conventional systemic chemotherapy and immunotherapy affords limited effectiveness and frequently compromises the quality of life for patients. Indeed, with systemic chemotherapy, the oncologist (and the patient) often walks a fine line between attempting tumour remission with prolonged survival and damaging the patient's vital functions to the point of death. In this context, it has probably been obvious for more than 100 years, due in part to the pioneering work of Ehrlich (1878), that targeted or localized drug delivery should be a major goal of chemotherapy. However, there is still only limited clinical use of nonsystemic intratumoral chemotherapy for even those high mortality cancers which are characterized by well defined primary lesions i.e. breast, colorectal, lung, prostate, and skin. There has been a proliferation of intratumoral chemotherapy and immunotherapy research during the past two to three years. It is therefore the objective of this review to focus much more attention upon intratumoral therapeutic concepts which could limit adverse systemic events and which might combine clinically feasible methods for localized preoperative chemotherapy and/or immunotherapy with surgery. Since our review of intratumoral chemoimmunotherapy almost 20 years ago (McLaughlin & Goldberg 1983), there have been few comprehensive reviews of this field; only one of broad scope (Brincker 1993), three devoted specifically to gliomas (Tomita 1991; Walter et al. 1995; Haroun & Brem 2000), one on hepatomas (Venook 2000), one concerning veterinary applications (Theon 1998), and one older review of dermatological applications (Goette 1981). However, none have shed light on practical opportunities for combining intratumoral therapy with subsequent surgical resection. Given the state-of-the-art in clinical and surgical oncology, and the advances that have been made in intratumoral drug delivery, minimally invasive tumour access i.e. fine needle biopsy, new drugs and drug delivery systems, and preoperative chemotherapy, it is timely to present a review of studies which may suggest future opportunities for safer, more effective, and clinically practical non-systemic therapy.