Diagnosis and treatment of the inferior vena cava syndrome in advanced malignant disease.

The syndrome of intrahepatic inferior vena cava obstruction has neither been commonly recognized nor adequately described. Symptoms include the abrupt onset of ascites, hepatomegaly, and fluid retention below the diaphragm with edema of the lower extremity. Proteinuria can be associated with these symptoms. When this syndrome has been caused by malignant hepatic enlargement, it has not been well characterized in the literature, and its treatment has been ignored. We have diagnosed the inferior vena cava syndrome due to metastatic liver involvement in 34 patients before death. Thirty-three of these patients were treated using a combination of strip radiotherapy to the hepatic vena cava, with or without hepatic arterial infusion of chemotherapy. Fifty-six percent of the patients completed a full course of radiotherapy, with an 83 percent response rate. A dose of 3,000 to 4,500 rads was found to be safe and provided excellent palliation of ascites and edema. Tumors known to be radiosensitive had the best responses and side effects were few and mild in nature. Recognition and treatment of this condition will assume greater importance as survival is prolonged in more patients with advanced malignancy.

The importance of treatment sequence in advanced and metastatic carcinoma of the breast.

From 1965 to the present, 287 patients with advanced and metastatic carcinoma of the breast have been treated according to a uniform philosophy of sequential therapy. Surgical castration was the initial procedure for premenopausal women and for postmenopausal women with clinical or laboratory evidence of endocrine responsive tumors. Tumor progression following castration was treated with major endocrine ablation, either adrenalectomy or hypophysectomy. Patients who relapsed following major ablation were treated with antiestrogen therapy as it became available. Nonresponders to major ablation and patients relapsing after antiestrogen therapy were treated with combination chemotherapy including cytoxan, methotrexate, 5-fluorouracil, and vincristine followed by adriamycin alone or in combination. Progression following chemotherapy was treated with additive hormonal therapy. Radiation therapy was used throughout for the control of localized disease, usually following complete hormonal ablation, except in cases of brain and spinal metastatic disease. The median survival for the entire group was 40.5 months from the onset of metastatic disease. Patients who responded to both oophorectomy and major ablation had a median survival of 61 months, which compares favorably to survival of 14 to 22 months reported in major combination chemotherapy trials. Survival following this method of sequential therapy is superior to other plans of management.

Results of oophorectomy by menstrual and estrogen receptor states in patients with metastatic breast cancer.

The records of 204 women with metastatic breast carcinoma treated by oophorectomy were analyzed. Premenopausal women had a response rate of 50 percent. Forty-one percent of postmenopausal women responded. Those who responded had an average duration of response of 22 months and a length of survival twice that of the nonresponders. There was a better than 60 percent correlation between response to oophorectomy and response to further endocrine ablation. Response to endocrine manipulation is more a function of the hormonal sensitivity of the carcinoma than of menopausal status.

Dimethyltriazenoimidazole carboxamide therapy of islet cell carcinoma of the pancreas.

Four patients with metastatic glucagonoma and one patient with metastatic diarrheogenic islet cell carcinoma of the pancreas were treated with dimethyltriazenoimidazole carboxamide (DTIC), 250 mg/M2 daily for five days repeated every four weeks. All patients responded clinically and chemically in one or more ways by a reduction in plasma glucagon levels, improved glucose tolerance, decreased measureable tumor, weight gain, and resolution of necrolytic migratory erythema and diarrhea. This experience and other cases from the literature call for the investigation of DTIC as the initial therapy in metastatic islet cell carcinoma of the pancreas and as being of possible benefit in other tumors of neuroendocrine origin.

Endocrine ablation for metastatic breast cancer: a reappraisal of hormone receptors.

PIP: Other indicators of hormone sensitivity, besides estrogen receptor (ER) content, such as response to oophorectomy, antiestrogens, prolactin suppression, and correlation with progesterone receptors (PR), were evaluated in the hope of further improving selectivity and response of patients undergoing endocrine ablation for metastatic breast cancers. 225 patients have undergone full endocrine ablation in the last 30 years at this hospital, 208 by adrenalectomy and 17 by hypophysectomy. 206 of these patients could be retrospectively reviewed, and of these there were objective responses to therapy in 50% of patients. ER analyses were performed in 1 or more breast cancer specimens in 113 of these patients. ER study showed that a patient who was ER+ and responded to a functional test of endocrine sensitivity had a 70-80% chance of also benefiting from adrenalectomy or hypophysectomy. Conversely, patients with absent or unknown hormone receptors who failed therapeutic trials of endocrine sensitivity had little or no chance of responding to major ablation; these cases are best treated with multiagent chemotherapy. The value of sequentially treating selected patients with endocrine manipulation in addition to chemotherapy was also studied. Patients who failed to respond to endocrine manupulation survived slightly over 2 years on chemotherapy, whereas patients who responded to major ablation lived with metastases an average of 4 years, whereas complete responders lived with metastatic disease an average of 6 years. By life table analysis, total survival of ER+ vs. ER- patients as well as responders vs. nonresponders was highly significant^ieng

5-FU versus combination therapy with tubercidin, streptozotocin, and 5-FU in the treatment of pancreatic carcinomas: COG protocol 7230.

From May 1972 until May 1976, 105 patients were entered on Central Oncology Group protocol 7230 to compare the combination of streptozotocin, tubercidin, and 5-fluorouracil (5-FU) versus 5-FU alone in the treatment of adenocarcinoma and islet cell carcinoma of the pancreas. Twenty-nine were not evaluable. Thirty-six evaluable cases received 5-FU, and 40 received the combination, with no significant difference in time to progression or survival. Toxicity in the two regimens was somewhat different but was essentially similar in magnitude. Results indicate no benefit in the treatment of adenocarcinoma of the pancreas with the three-drug combination over 5-FU alone. All of the islet cell tumor patients benefited from the combination by response or arrest of progression of disease. Further study should be directed toward the use of this combination in the treatment of functioning and non-functioning islet cell tumors of the pancreas.

Hyperdibasicaminoaciduria, hyperammonemia, and growth retardation: Treatment with arginine, lysine, and citrulline.

A 9-year-old girl with hereditary dibasicaminoaciduria has been studied for three years. Initially, clinical features were: growth failure; anorexia and aversion to protein, spontaneous daily protein intake averaging only 10 gm; fasting and postprandial venous hyperammonemia; subnormal plasma concentrations of lysine, arginine, ornithine, and citrulline, with generalized hypermonobasicaminoacidemia; abnormally high renal clearances of lysine, arginine, and ornithine; and intestinal malabsorption of lysine and arginine. Intestinal absorption of citrulline, a precursor of arginine and ornithine, was normal. The patient was observed during four sequential 6-month periods as follows: no treatment (Period I); dietary supplement of arginine and lysine (Period II); dietary supplement of citrulline and lysine (Period III); no treatment (Period IV). During Periods II and III growth rate increased 3- to 4-fold, spontaneous protein intake increased 2- to 3-fold, and abnormalities in blood NH3 and the plasma aminogram were partially corrected. In most respects the citrulline plus lysine supplement was more beneficial than that of arginine plus lysine.