One-hundred-ninety-four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high-dose (6000 rads) radiation therapy alone, to moderate-dose (4000 rads) radiation + 5-fluorouracil (5-FU), and to high-dose radiation plus 5-FU. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5-FU-containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5-FU and 6000 rads plus 5-FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level.

One hundred seventy-nine patients with advanced measurable colorectal cancer not previously treated with chemotherapy were entered into a prospective randomized clinical trial by the Mid-Atlantic Oncology Program (MAOP) to compare two schedules of delivery for single-agent fluorouracil (5-FU). The "standard" treatment was a schedule commonly employed in clinical practice, namely, a daily bolus dose administered intravenously (IV) for five consecutive days and repeated at 5-week intervals. The investigational treatment was a continuous infusion of 5-FU administered 24 hours a day for a protracted time (10 weeks or more). Both treatments were continued until the development of disease progression or unless interrupted for toxicity. Using stringent objective criteria requiring independent confirmation of x-ray or scan-documented response, the tumor response rate reached 7% (six of 87) for the bolus arm and 30% (26 of 87) for the infusion arms (P less than .001). Toxicity was substantially different for the two arms with major leukopenia observed only on the bolus arm, 22% developing grade 3 (severe) or grade 4 (life-threatening) leukopenia with four sepsis-related deaths. Hand-foot syndrome was observed only in the infusional arm, requiring treatment interruptions and dose reductions in 24% of patients, but with little impact on quality of life. In spite of the major difference in objective response rate, overall survival for the two groups was comparable. Administration of 5-FU as a continuous infusion for protracted periods clearly improves the therapeutic index for this agent in patients with advanced colon cancer with respect to response rate and reduced toxicity. This schedule appears workable in the community setting and yields response rates similar to those reported for 5-FU with high-dose leucovorin, but without the gastroin testinal toxicity profile of the latter combination.

For some tumors, cisplatin appears to be superior to carboplatin in terms of therapeutic effectiveness (germ cell tumors, bladder cancer, head and neck cancer), while for others, effectiveness is comparable (lung cancer, ovarian cancer). Toxicity profiles are distinctly different for the two analogues however, generally favoring carboplatin. The issue of potential carboplatin underdosing related to the lack of physiologic dose calculations (utilizing the AUC [area under the curve] method) in the comparative trials of cis- versus carboplatin is probably not clinically important since a dose response effect has not been established for carboplatin or for cisplatin. The selection of the optimal platinum analogue to be employed is dependent on the type of tumor, the treatment intention (palliative vs. curative) and the other component drugs being used in combination.

A totally implanted subclavian venous access system composed of a reservoir and silastic catheter was employed in 92 patients receiving infusion chemotherapy and/or hyperalimentation. The major catheter complication was subclavian or jugular vein thrombosis observed in 15 patients (16%). Thrombosis was observed in the ipsilateral subclavian or jugular vein surrounding the catheter without restricting function, except in two patients with thrombosis in the vein at the end of the catheter. Prophylaxis with low-dose Coumadin was effective in preventing thrombosis in high-risk patients as defined by a history of prior thrombosis. Streptokinase and/or heparin relieved the signs and symptoms of thrombosis, but clot dissolution or reversal of collateral flow was not observed. Explantation of the catheter was not necessary in all patients in that embolic complications of the thrombosis were not observed, and the system was retained and functioned in five patients in spite of the presence of thrombosis around the catheter. Other complications of the implanted system include "pocket" infection, catheter migration, and occlusion. Most complications may be managed without obligate catheter removal.

5-FU CI is superior to 5-FU bolus in terms of tumor response and achieves a slight increase of overall survival. The hematologic toxicity is much less important in patients who receive 5-FU CI, but hand-foot syndrome is frequent in this group of patients.