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The nutritional and immunological status of 140 malnourished cancer patients who were to receive intravenous hyperalimentation (IVH) were evaluated prior to treatment with IVH and chemotherapy (CMX), surgery or radiation therapy (XRT). Subsequently, these indices were correlated with responses to treatment. Cell-mediated immunocompetent (CMI+) patients (41%) had lost an average weight of 10 +/- 2.2 lbs., while cell-mediated immunoincompetent (CMI-) patients (59%) had lost an average weight of 31 +/- 2.5 lbs. (p less that 0.05). Total lymphocyte count (TLC) averaged 1290 +/- 250 cells/mm3 in CMI+ patients and 900 +/- 140 cells/mm" in CMI- patients (p less than 0.05). Serum albumin concentration (SA) was 3.6 +/- 0.06 g/dl in CMI+ patients and 3.3 +/- 0.05 g/dl in CMI- patients (p less than 0.05). In the CMI+ group, 49% had a positive response to CMX, whereas only 27% of the CMI-group responded to CMX (p less than 0.01). In the surgery group, 88% of the CMI+ patients, but only 65% of CMI- patients, had uncomplicated postoperative recovery periods. Although nutritional repletion with IVH was undertaken in all patients, those patients with initial CMI- responses had greater body weight loss, lower SA and TLC and either a decreased response to CMX or an increase in postoperative morbidity and mortality when compared with patients who initially had CMI+ responses.

In over 1000 cancer patients treated with intravenous hyperalimentation (IVH), tumor growth has not been identified and catheter-related sepsis has been minimal. Studies in rats demonstrated that the host benefits more than the tumor during nutritional repletion, and any stimulation of tumor growth in the rat-tumor model could be manipulated with DNA specific drugs to benefit the host. A study of 65 malnourished cancer patients undergoing oncologic therapy and treated with IVH indicated that much of the immune suppression in these patients was the result of malnutrition coincident with or secondary to oncologic treatment. Conclusions reached in this study were that nutritional repletion resulted in a return of skin test reactivity, proper wound healing in the surgical patient, and possibly an increase in response to chemotherapy. Certainly, the use of IVH allowed specific oncologic therapy to be administered to a group of malnourished patients who otherwise might not have been acceptable candidates for intensive antineoplastic therapy.

Potential hepatotoxicity from systemic hyperthermia (43 degrees C) +/- simultaneous hepatic artery infusion with 5-FU was evaluated in an animal model. Twenty-two dogs had aorta-vena caval shunts (8 mm Dacron grafts) placed, and 10 of these dogs had silastic catheters inserted in their hepatic arteries. Two weeks later, Group I (n = 8) was heated to 43 degrees C for one hour (distal esophageal + intrahepatic temperature) using the shunts and blood-heat exchangers; Group II (n = 6) was heated to 43 degrees C for one hour with simultaneous intrahepatic infusion of 5-FU (10 mg/kg); Group III (n = 8) was shamheated (37 degrees C) and underwent a one hour intrahepatic infusion with 5-FU (10 mg/kg). Serum alkaline phosphatase, SGOT, SPGT (IU/ml) and bilirubin were measured, and liver biopsies were obtained at 0 and 1 hour, at one and seven days. Mean SGOT levels increased significantly (P less than 0.05) in Group II from 19 +/- 2 to 31 +/- 6 and 63 +/- 18 at one hour and one day; these levels rose slightly in Group I from 31 +/- 5 to 40 +/- 8 and 47 +/- 8 at one hour and one day. Hepatocellular enzyme levels returned to normal at seven days in both groups. Mean SGOT and SGPT levels remained similar in Group III at all time periods. No significant differences in mean serum alkaline phosphatase or bilirubin levels were noted. There was no histologic evidence of hepatocellular necrosis at any time period. Survival was 6/8, 5/6 and 8/8 dogs in Groups I, II, and III, respectively. Systemic hyperthermia to 43 degrees C for one hour in dogs does not adversely affect serum hepatic enzymes or cell structure; reversible serum hepatic enzyme changes occurred when hyperthermia was combined with hepatic artery infusion with 5-FU.

Serum zinc concentrations were determined in 26 extensive squamous cell lung cancer patients and were tested for correlations with survival, response to therapy, nutritional status indices, and various host defense characteristics. Subnormal serum zinc levels were found in 24 of the 26 patients. The mean serum zinc concentration was 43.2/micrograms 100 ml +/- 3.6 S.E.M. (normal = 80-100 micrograms/100 ml). A significant (P = 0.007) survival advantage was demonstrated for those patients with pretreatment zinc concentrations greater than 45 micrograms%, but serum zinc levels did not correlate with response to chemotherapy (also significantly affecting survival). Decreased serum zinc concentrations were significantly associated with decreased neutrophil migration measured by the skin window technique and with decreased triceps skin fold thickness but not with any of the other host defense and nutritional induces measured. These data suggest that further studies are indicated to examine the role of serum zinc concentration as a possible sensitive prognostic characteristic and to determine if zinc administration may be of therapeutic benefit in cancer patients.

Intravenous hyperalimentation was utilized to support nutritionally 23 malnourished patients with major head and neck tumors during surgical treatment, radiotherapy, or the convalescent period. Fifteen patients were treated during the perioperative period and 12 survived. Six patients received convalescent nutritional support successfully 4 to 24 months following operation or radiation treatment. Two patients received treatment with hyperalimentation throughout a protracted course of radiation therapy. Weight gain, wound healing, and recovery were achieved in all but 3 patients. Subclavian vein thrombosis occurred in 1 patient, and catheter-related sepsis occurred in 2 patients. Otherwise, hyperalimentation was safe and efficacious in the debilitated patients. These patients may now become acceptable risks for surgical treatment or radiation therapy by nutritional repletion with intravenous hyperalimentation.

Host and tumor response to methotrexate (MTX) was studied in 122 tumor-bearing, malnourished rats during nutritional repletion. Sprague-Dawley rats with transplanted Walker-256 carcinosarcoma were fed a regular diet (RD) for five days followed by a protein-free diet (PFD) for ten days. On day 15, one group was orally repleted with a regular diet, while the other group continued on PFD. Methotrexate (20 mg/kg) therapy was begun in RD groups either on day 17 or day 21. Similarly, MTX (20 mg/kg) was begun in PFD groups either on day 17 or day 21. Untreated (no MTX) rats served as control animals and gained more body weight than MTX-treated rats. Tumor weight (TW) to carcass weight (CW) ratios were significantly less in both PFD and RD groups when MTX was given two days after dietary manipulation compared with results when MTX was given six days after dietary manipulation. Maximum tumor inhibition by MTX (least change in tumor diameter compared with control rats) was significantly greater when MTX was given to nutritionally repleted animals compared with results when MTX was given to animals continued on the protein-free diet. Dietary protein depletion inhibited tumor growth and tumor response to methotrexate. Nutritional repletion stimulated host and tumor growth. A short period of nutritional repletion (two days) prior to MTX chemotherapy resulted in improved host nutritional status and maximum tumor inhibition.

Radiation therapy may induce anorexia with resultant weight loss and inanition that can limit the dose of radiation therapy administered. The purpose of this study was to evaluate 39 nutritionally-depleted patients who had a variety of malignant diseases treated with radiation therapy and concomitant nutritional support with intravenous hyperalimentation (IVH). The average dose of radiation delivered was 3827 rads in an average of 3.5 weeks. Ninety-five percent of the patients completed their planned course of radiation therapy and improved symptomatically. Fifty-four percent of the patients responded with a greater than 50% reduction in tumor size. Responding patients gained an average weight of 13.0 +/- 6.5 lbs. during IVH (av. 36.2 days) and radiation therapy (av. 3832 rads), whereas non-responding patients gained only 4.9 +/- 8.8 lbs. (p less than 0.001) during IVH (av. 42.8 days) and radiation therapy (av. 3819 rads). Serum albumin concentrations rose from 3.12 +/- 0.49 gm/100 ml to 3.51 +/- 0.68 gm/100 ml (p less than 0.05) during treatment in responding patients but did not rise significantly from 3.09 +/- 0.48 gm/100 ml in non-responding patients. In conclusion, IVH allowed a planned course of radiation therapy to be delivered to a group of poor-risk, malnourished cancer patients, and a positive correlation between tumor response and nutritional status was identified. Moreover, IVH was a valuable adjunct in the treatment of six patients who had enteric fistulas that originated from radiated bowel.

Ten consecutive malnourished patients with undifferentiated squamous cell carcinoma of the esophagus underwent operation for colon interposition. They received intravenous hyperalimentation preoperatively and/or postoperatively for an average time of 21.5 days and had an average weight gain of 6.5 lb. There was no significant gastrointestinal morbidity, but one patient succumbed to aspiration pneumonia. All ten patients had postoperative gastrografin swallow radiography which showed no leaks in either anastomosis. With proper use of intravenous hyperalimentation, morbidity and mortality following colon interposition in the malnourished patient for either palliative or curative bypass can be decreased to acceptable levels.