Pain management in the opioid-addicted patient with cancer.

Two patients with an active or recent history of opioid abuse had painful complications of cancer that required narcotic analgesic therapy. Initial pain management was difficult due to issues of distinguishing tolerance from disease progression, concurrent methadone maintenance, and drug-seeking behavioral patterns. Pain control was achieved with psychological support, medication contracts, and attention to proper dosing of opioids. Suggested guidelines for management of these cases are offered.

Phase I trial of 5-fluorouracil and recombinant alpha 2a-interferon in patients with advanced colorectal carcinoma.

We have previously shown that the combination of 5-fluorouracil (5-FUra) and recombinant alpha-2a-interferon (rIFN-alpha-2a) produced objective responses in 23 of 32 (63%) previously untreated patients with advanced colorectal carcinoma. Because in vitro data suggest that rIFN-alpha-2a modulates the cytotoxic effects of 5FUra in a concentration-dependent manner, a phase I clinical trial was initiated to determine the maximum tolerated dose of rIFN-alpha 2a when administered in combination with 5FUra. A total of 27 patients with advanced colorectal carcinoma were enrolled. The median age was 64 years, and the median performance status was 1. A total of 18 patients had no prior chemotherapy and 19 no prior 5FUra. 5FUra was administered at 750 mg/m2/day by continuous i.v. infusion for 5 days, followed by weekly bolus therapy. rIFN-alpha 2a was administered at 6, 9, 12, 15, or 18 x 10(6) units s.c. beginning on day 1. The dose-limiting toxicity of this regimen was fatigue, resulting in a decrease in performance status, and this was the only toxicity that correlated with increasing dose of rIFN-alpha 2a. Eastern Cooperative Oncology Group grade 3-4 toxicities included leukopenia (6), thrombocytopenia (2), anemia (4), stomatitis (4), diarrhea (4), neurological (2), infection (2), and allergy (2). Three quarters of the patients required interruption of therapy or dose reductions of either 5FUra or rIFN-alpha 2a for toxicity. Among the patients with measurable disease who were previously untreated with 5FUra, 5 of 9 at the lowest dose levels achieved an objective response, including one pathological complete responder, whereas 0 of 9 at the three highest dose levels responded. Among patients previously treated with 5FUra, only 1 achieved an objective response. We conclude that the maximum tolerated dose of rIFN-alpha 2a, when administered with 5FUra as above, is 15-18 x 10(6) units; however, the efficacy of this regimen does not appear to be related to the dose intensity of rIFN-alpha 2a, and future regimens should employ a lower dose, intermittent schedule of rIFN-alpha 2a, which may be better tolerated.

Fluorouracil and recombinant alfa-2a-interferon: an active regimen against advanced colorectal carcinoma.

Based on in vitro studies that have demonstrated synergy between recombinant alfa-2a-interferon (rIFN alpha-2a) and the fluoropyrimidine, fluorouracil (5FU), against two human colon cancer cell lines, a pilot clinical trial was initiated to determine the effects of the combination of 5FU and rIFN alpha-2a in patients with advanced, unresectable colorectal carcinoma. A total of 30 patients were enrolled; all were evaluable. 5FU was administered as a loading course, 750 mg/m2 daily for 5 days by continuous infusion followed by weekly bolus therapy, rIFN alpha-2a, 9 MU, was administered subcutaneously three times per week. Of 17 previously untreated patients evaluable for response, 13 achieved a response. Three patients had disease progression. No previously treated patients had a major response. There was one death clearly related to therapy, an event preceded by watery diarrhea and neutropenic sepsis. Other toxicities were reversible and responded to dose reduction. With a median follow-up of 16+ months, median survival has not been reached among the previously untreated patient cohort. We conclude that the combination of 5FU and rIFN alpha-2a is an active regimen against disseminated colorectal cancer in previously untreated patients.

Clinical toxicities of the combination of 5-fluorouracil and recombinant interferon alfa-2a: an unusual toxicity profile.

Recombinant interferon (rIFN) modulates the cytotoxic effects of the fluorinated pyrimidine, 5-fluorouracil (5FU), in in vitro experimental tumor cell systems. In three clinical trials employing rIFN and 5FU in patients with advanced colorectal carcinoma conducted at the Albert Einstein College of Medicine, more than half the patients achieved an objective response. Of interest, the clinical spectrum of toxicities observed with this combination is different from those seen with either rIFN or 5FU alone. This novel constellation of toxicities includes a clinical syndrome characterized by watery diarrhea followed by life-threatening sepsis. Thus, careful observation and characterization of these toxicities are required. Patient education, with the goal of making patients recognize serious side effects, is important in the management of these patients.

Recent advances in the management of biotherapy-related side effects: fatigue.

Limited information about fatigue patterns in patients with cancer exists in the biotherapy literature. When fatigue is mentioned, it is usually to state whether or not it was a dose-limiting side effect. No further data are provided on how fatigue was measured; which patterns were noted and when; and which relationships were found between fatigue and demographic characteristics, type of biologic response modifier, route of administration, or cumulative dose. Thus, there is little available in the biotherapy literature to guide nursing practice in managing this side effect. Theory that guides practice, however, often emanates from the personal experiences of the patients and from the clinical observations and intuitive hunches of the nurses and physicians participating in clinical trials. These individuals have been most generous in sharing their insights and unpublished data with the authors. This paper presents a comprehensive view of current knowledge on fatigue to guide present nursing practice with patients receiving biotherapy and to provide direction for future nursing and clinical trial research.