Donald R. Cole

A five year progress report on the effectiveness of intraluminal chemotherapy (5-fluorouracil) adjuvant to surgery for colorectal cancer

Abstract 1. 1. Nationwide survival rates after surgery for cancer of the colon and rectum have not improved in the past twenty years. 2. 2. The modes of spread of cancer of the colorectum are now well known. 3. 3. A new combined surgical, intraluminal, and systemic chemotherapy regimen has been evolved in our clinic, hopefully to inhibit tumor spread along these pathways and thus enhance survival rates. 4. 4. A five year clinical experience using 5-FU intraluminally and systemically has been computer-analyzed. 5. 5. No apparent improvement in survival rates in stage I and II cases (negative nodes) was indicated in the 5-FU treated group versus nationwide averages. 6. 6. In the positive node group (stage III) the most significant improvement seemingly develops. At five years the cumulative proportion survival rate is 65 per cent for the 5-FU treated group versus 32 per cent in the nationwide (control) series and 26 per cent in the St. Vincents Hospital (control) series. 7. 7. This is only a probing study. The authors well recognize the statistical pitfalls of such a small series of cases in a single institution. 8. 8. Hopefully a multihospital cooperative project with a double blind randomized study design may be achieved, utilizing upwards of 150 cases yearly.

Intraluminal chemotherapy (HN2 or 5-FU) adjuvant to operation for cancer of the colon and rectum. II. Follow-up report of 97 cases.

This is a five‐year progress report of a method of intraluminal chemotherapy adjuvant to operation for cancer of the colon and rectum. The technique involves sequestering the diseased segment between tape ligatures. A cancericidal drug is then injected into the lumen within the taped area. The clamping of the pedicle vessels is designedly delayed 30 minutes to allow maximum dosage absorption. In the 5‐FU group, the agent is repeated intravenously on postoperative days 1 and 2. A total of 97 patients were followed up to five years in the treated series and 268 patients were followed in the control series. HN2 and 5‐FU were used. There was no significant rise in morbidity or mortality associated with the technique. Survival follow‐up studies of the HN2‐treated group at the end of five years shows no improvement over the controls. However, in the 5‐FU‐treated group of patients the increased trend in survival noted at three years continues to be sustained at four years.

Absorption patterns of intraluminal injected nitrogen mustard in the isolated right colon of the dog

Summary Absorption patterns of local intraluminal injection of an anti-cancer drug have been studied in 37 dogs. These experiments demonstrate that injection of a high concentration of HN 2 into the isolated right colon will result in a high local concentration, plus appreciable sustained venous and lymphatic absorption. It is hoped that this type of perfusion technique might reduce the incidence of surgically induced spread of cancer, with subsequent local and distant tumor implants.

Intraluminal chemotherapy with nitrogen mustard in simulated cancer of the colon in the rat

Summary o 1. Implantation of Walker 256 carcinosarcoma in the cecal pouch of the rat has produced a simulated cecal cancer. 2. Intraluminal use of HN2 as an adjuvant to resection of the cecal pouch Walker 256 carcinosarcoma in the rat has resulted in a reduction from 42 per cent to 20 per cent in the incidence of local suture line recurrence.

Intraluminal cancer chemotherapy adjuvant to pulmonary resection

Summary A method has been developed in an attempt to reduce cancer cells spread at the time of surgery for lung cancer. The technique is simple, inexpensive and not time consuming. In the dog, we have demonstrated that at 0.4 mg/kg. and 0.8 mg./kg. of HN2 a high local dose can be achieved with a low systemic concentration. To date, our work has been done on dogs but it is our plan to adapt the technique and apply it carefully to humans in the treatment of lung cancer.