Herbert C. Hoover

Obstacles to implementing cancer clinical trials

There are numerous obstacles to implementing and conducting clinical trials. Patient accrual and the costs of clinical trials are difficult problems for researchers. Additional obstacles to implementing clinical trials are patient-related, physician-related, and nurse-related barriers.

Active specific immunotherapy with autologous tumor cell vaccines for stage II colon cancer: logistics, efficacy, safety and immunological Pharmacodynamics.

In the area of cancer treatment, immunotherapy with vaccines has suffered in the last 5 years, due to many clinical trial failures. One must keep in mind however, that many of the clinical trials conducted in the past decade were performed without the benefit of sound regulatory guidance or validated and compliant manufacturing processes. This has clearly been the case for patient specific, tumor cell vaccine therapy. The safety concerns that emanated within the regulatory agencies from the Somatic Cell Therapy concepts, translated to active specific immunotherapy with vaccines. Fortunately, in the past 5 years advances in understanding the immune system, improved design of clinical trials, improvement and compliance of manufacturing processes provided opportunities to significantly improve efficacy and safety. Clearly, the vaccine research establishment has learned the importance of not just selecting antigens but the requirement of tumor associated immunogens that can stimulate a functional immune response. Also, it has become clear that immunotherapy works best in situations of minimal residual disease. Finally, more realistic endpoints in clinical trials have been recognized and accepted by oversight review committees. This commentary describes the “trials and tribulations” of developing a patient specific, autologous tumor cell vaccine for therapy of Stage II colon cancer.

Recent Developments in the Surgical Management of Rectal Carcinoma

The introduction of the circular stapler has made sphincter-sparing resection of middle to lower rectal cancer considerably easier and safer for most surgeons. Fewer patients today require abdominoperiheal resection and a permanent abdominal stoma. Most studies suggest that local recurrence and survival rates have not been adversely affected by the trend toward sphincter preservation as long as an adequate resection can be accomplished. I Just what represents an acceptably wide resection remains debatable, but most would agree that a distal margin of 2 cm is adequate for most cases. A less well accepted or less widely known concept is the importance of a sharp dissection of the entire mesorectum in patients with potentially curable middle to lower rectal cancers. The British, particularly Heald et al, 2,3 have led the way in stressing the great importance of the mesorectum in rectal cancer. Their careful pathologic studies have clearly shown that lymphatic spread, although rarely beyond 1 to 2 cm intramurally, can be up to 5 cm distal in the mesorectum. The conventional blunt mobilization of the posterior rectum is discouraged for fear that tumor lymphatics or veins could be torn, or that the tumor itself could be inadvertently exposed. Sharp dissection would reasonably be expected to be less traumatic. Heald has stressed his conviction that distal spread of rectal