Future directions in the therapy for large bowel cancer.

The essence of clinical research success is a blending of modality-oriented development and disease oriented strategy. Development therapeutics begins with single institution pilot, or exploratory, studies in which the treatment itself is more important than the strategic approach to the disease(s) being treated. Ultimately, if the exploratory studies are encouraging, the confirmatory and explanatory studies (Phase II--III) which follow will be disease oriented. Advances in the treatment of colorectal cancer will, it is hoped, come from new developmental therapeutics in chemotherapy, radiation therapy and biologic response modifier therapy. Developments in chemotherapy involve a steady stream of new drugs which are entering clinical trial from the drug development program of the NCI as well as from the pharmaceutical industry. These drugs include new structures and analogues of structures known to be active in some tumor types. In the latter category particular emphasis is being placed on new anthracycline analogues of doxorubicin and analogues of cisplatinum diammine dichloride. Recognizing the importance of colorectal cancer experimental models for this tumor are being given prominence in the prediction for now active drugs. These include transpantable rodent colon tumors and human colon tumors grown in nude mice or in a subrenal capsule system. In addition, the clonogenic assay of human tumor stem cells is under active investigation. It is hoped that this assay will be able to help predict which patients with colorectal tumors will respond to the given available drugs, and help predict the selection of new active drugs for colorectal cancer. Examples of new developments in radiation oncology which may have eventual impact on large bowel cancer include: (1) high linear energy transfer deliverence techniques such as neutrons, heavy ions and pi-mesons; (2) radiation sensitizers such as misonidazole, desmethylmisonidazole and newer electronic affinic compounds; (3) radiation protectors such as WR-2727; and (4) new fractionation schedules. In addition hyperthermia is evolving as a viable approach to killing neoplastic cells both alone and in conjunction with x-ray therapy. The biologic response modifiers (BRM) are a new and exciting development in cancer treatment. These are materials which hopefully will modify the hosts ability to react to neoplastic cells in a way which will be of therapeutic benefit either by itself or in conjunction with other therapies. Among BRMs of current interest are the interferons and thymic hormones. The interferons have demonstrated some ability to shrink clinically evident breast cancers and lymphomas and when supplies permit studies in bowel cancer will be great interest.