John F. Foley

A phase III trial on the therapy of advanced pancreatic carcinoma evaluations of the mallinson regimen and combined 5-fluorouracil, doxorubicin, and cisplatin

One hundred eighty‐seven patients with histologically proven advanced pancreatic adenocarcinoma were randomly assigned to therapy with 5‐fluorouracil (5‐FU) alone, to the Mallinson regimen (combined and sequential 5‐FU, cyclophosphamide, methotrexate, vincristine, and mitomycin C), or to combined 5‐FU, doxorubicin, and cisplatin (FAP). Patients with both measurable and nonmeasurable disease were included and the primary study end point was survival. Among 41 patients with measurable disease, objective response rates were 7% for 5‐FU alone, 21% for the Mallinson regimen, and 15% for FAP. The median interval to progression for each of the three regimens was 2.5 months. Survival curves intertwined with the median survival times for 5‐FU alone and the Mallinson regimen at 4.5 months and for FAP at 3.5 months. Compared with 5‐FU alone, both the Mallinson regimen and FAP produced significantly more toxicity. Neither the Mallinson regimen nor FAP can be recommended as therapy for advanced pancreatic carcinoma. Any chemotherapy for this disease should remain an experimental endeavor.

A randomized, crossover evaluation of methylphenidate in cancer patients receiving strong narcotics

Sedation may be a doselimiting side-effect of opioid therapy in some cancer patients. This study was designed to evaluate further the use of the psychostimulant, methylphenidate, an agent that has been reported to counteract opioid-induced sedation, in patients with cancer-related pain. Patients receiving a stable dose of an opioid for cancer-related pain were recruited for this randomized, double-blind, crossover clinical trial. In addition to their regular dose of narcotics, they received 5 days of methylphenidate followed by 5 days of placebo, or vice versa. Our data did not definitively demonstrate any statistically significant benefit for methylphenidate, but did suggest that this drug could mildly decrease narcotic-induced drowsiness and could increase night-time sleep. These data, in conjunction with other published data, suggest that methylphenidate can counteract narcotic-induced daytime sedation to a limited degree.

A prospective, randomized evaluation of intensive‐course 5‐fluorouracil plus doxorubicin as surgical adjuvant chemotherapy for resected gastric cancer

This study evaluated combined 5‐fluorouracil (5FU) and doxorubicin as postoperative adjuvant chemotherapy for patients who had undergone potentially curative resection of a primary gastric adenocarcinoma. One hundred twenty‐five eligible and evaluable patients were stratified according to extent of surgical resection, location of the primary tumor within the stomach, and lymph node status. They were then randomized to either receive three cycles of chemotherapy or be observed. The median time from patient entry was 7 years. Results showed no significant difference in time to recurrence. The 5‐year survival rate was 33% for the observation arm and 32% for the adjuvant therapy arm. The data excluded a 16% improvement in the 5‐year survival rate for patients receiving chemotherapy with a P value less than 0.05. There were two drug‐related fatalities due to sepsis. These results demonstrate no substantive benefit for this chemotherapy regimen as postoperative adjuvant treatment of resected gastric cancer.

Therapy of malignant APUD cell tumors: Effectiveness of DTIC

Eleven patients with malignant APUD tumors, five islet cell carcinomas, five carcinoid tumors and one medullary carcinoma of the thyroid were treated with DTIC. Nine of 11 patients benefitted from treatment. A literature review revealed that other APUD tumors responded when treated with DTIC. DTIC is a useful agent for treatment of malignant APUDomas, and may be the drug of choice for islet cell carcinoma of the pancreas.

Evaluation of external-beam radiation therapy plus 5-fluorouracil (5-FU) versus external-beam radiation therapy plus hycanthone (HYC) in confined, unresectable pancreatic cancer☆

From March 1981 to November 1987, 87 patients with histologically confirmed pancreatic adenocarcinoma, unresectable but confined to the pancreatic region, were randomized to two treatments. The standard treatment was 40-50 Gy external-beam radiation therapy (RT) to gross tumor plus potential microscopic tumor with a 5 Gy boost to gross tumor plus a 1.5-2.0 cm margin, using multiple fields and 5-fluorouracil (5-FU) 500 mg/m2/d intravenously by rapid infusion. The 5-FU was given each of the initial 3 days of each of three 20 Gy radiation courses. The experimental treatment used identical radiation fields, but the two Gy daily radiation fractions were administered in a continuous course to a total dose of 50 Gy. Hycanthone was administered 60 mg/m2 intravenously within 2 to 4 hr during each day of the 5-day course of infusions during the first and fifth weeks of radiation therapy. There was no statistically significant difference between treatment arms in survival (p = 0.82) or disease-free survival (p = 0.27). Seven percent of hycanthone-treated patients demonstrated hepatic toxicity which was usually mild in nature. There was, however, one death due to hepatic toxicity.

A double‐blind trial of tamoxifen plus prednisolone versus tamoxifen plus placebo in postmenopausal women with metastatic breast cancer. A collaborative trial of the north central cancer treatment group and mayo clinic

This trial was conducted to determine if the reported superiority of tamoxifen (TAM) plus prednisolone (PRDLN) over TAM alone in postmenopausal women with metastatic breast cancer could be corroborated. A total of 326 patients were randomized on a double‐blind trial to TAM (10 mg twice daily) plus placebo or TAM plus PRDLN (5 mg twice daily). Six patients (2%) were disqualified. Considering 256 patients with measurable or evaluable disease, objective responses were seen in 48 (38%) of 126 TAM patients and 61 (47%) of 130 TAM plus PRDLN patients (chi‐square, P = 0.15). Considering all 320 evaluated patients, median time to disease progression was 11 months for TAM and 10 months for TAM plus PRDLN (log rank, P = 0.81), and median survival time was 35 and 32 months, respectively (P = 0.40). Covariate analyses showed no significant association between treatment and outcome. Weight gain and edema were significantly greater with TAM plus PRDLN. The addition of PRDLN to TAM is not advocated for the management of postmenopausal women with metastatic breast cancer.

Blood histamine and solid malignant tumors

SummaryA clinical study was performed to determine whether patients with a newly diagnosed solid malignant tumor manifest an alteration in whole-blood histamine levels. Our results indicate that such patients have blood histamine nearly three times greater than either normal, healthy individuals or noncancerous disease controls. Following surgical removal of the tumor, blood histamine levels remained high for 2 months and then dropped close to the normal range 3 months after surgery. Basophil counts did not change significantly in the presence of a malignant tumor. Patients receiving either chemotherapy or radiation therapy, and terminal cancer patients who were no longer receiving any therapy except for pain control had blood histamine within or below the normal range. By analogy with animals studies, we suggest that nascent histamine synthesis is increased in the presence of a developing tumor. The clinical usefullness of this observation remains to be determined.

Improved palliation of pancreatic carcinoma

A retrospective study has been made of the diagnosis and treatment of 250 patients with carcinoma of the pancreas (confirmed by celiotomy, biopsy, and autopsy in 242) from a private surgical group at one hospital (Series A), a 12‐year medical‐surgical experience at a second private hospital (Series B), and a 10‐year experience at the University of Nebraska Hospital, which included a high percentage of low‐income referrals (Series C). Diagnosis was usually delayed until obstructive jaundice or radiologic evidence of upper gastrointestinal tract deformity existed, and was usually achieved by celiotomy. Follow‐up studies using second look operations and autopsies suggest that supervoltage radiation therapy to at least 3,000 rads tissue dose initial course combined with initial 5‐fluorouracil (FU), followed by weekly FU maintenance therapy, has at times favorably modified the course of the primary as well as locally metastatic carcinoma. Eight of nine patients whose erythrocytes were tagged with Cr51 for quantitative specific blood loss measurement excreted one or more stools significantly exceeding the normal 0.6 ± 0.4 ml lost per 24 hours; the ninth patient had complete biliary obstruction at the time of testing. In two patients, the blood loss was as high as 83‐239 ml daily due to extrinsic gastric invasion. In a third patient, the blood loss decreased from 50 ml daily to 4 ml daily during irradiation and FU therapy. Survivorship studies indicate no significant difference between Series A and C cases in this study, with the proportion of survivors at 6 and 23 months palliated by major surgical resection attempts beginning to be equalled at 23 months, by those who received only bypass operations combined with pancreatic irradiation to 3,000–4,000 rads and FU therapy. Patients over 45 with nonspecific digestive disturbances and negative endoscopic and radiologic examination with persistent daily gut blood loss by the radiochromium technique of 1.8 ml or greater for 2–3 weeks duration should have the level of bleeding identified either by sequential gastrointestinal intubation and serial aspiration of digestive secretions for blood loss measurement, or by radiologic methods, which are usually negative early in the growth of extra‐ampullary carcinomas.

Cutaneous necrotizing granulomatous vasculitis with evolution to T-cell lymphoma

The evolution of unusual cutaneous vasculitis to a systemic T cell lymphoma was observed over a 12-year period. Precise classification of the skin biopsy specimens during the course of this patients illness was difficult. Different observers suggested malignant hemangioendothelioma, malignant lymphoma, regressing atypical histiocytosis, and granulomatous vasculitis. In retrospect, the biopsy specimens likely represented the spectrum of cutaneous lymphomatoid granulomatosis. This condition is yet another example of a reactive lymphoid proliferation proceeding to a malignant lymphoma.

Influence of fibroblastic collagen and mucopolysaccharides on HeLa cell colonial morphology.

Abstract Human fibroblasts in vitro (a) synthesize collagen and acid mucopolysaccharides and (b) when grown together with HeLa cells, induce a change in the colonial morphology of the latter. This study demonstrates that the induction of colonial changes by the fibroblasts is not necessarily causally related to the production of collagen and acid mucopolysaccharides.