Rituximab therapy in hematologic malignancy patients with circulating blood tumor cells: association with increased infusion-related side effects and rapid blood tumor clearance.

PURPOSE: Rituximab was recently approved for use in relapsed, low-grade non-Hodgkin's lymphoma; however, few data exist regarding the safety of this agent in patients with a high number of tumor cells in the blood. METHODS AND RESULTS: After the observation at our institution of a rapid reduction of peripheral-blood tumor cells with associated severe pulmonary infusion-related toxicity in two patients with refractory hematologic malignancies, data on three additional cases were collected from physician-submitted reports of adverse events related to rituximab treatment. Five patients with hematologic malignancies possessing a high number of blood tumor cells were treated with rituximab and developed rapid tumor clearance. The median age was 68 years (range, 26 to 78 years). Patients were diagnosed with B-cell prolymphocytic leukemia (n = 2), chronic lymphocytic leukemia (n = 2), or transformed non-Hodgkin's lymphoma (n = 1). All of these patients had bulky adenopathy or organomegaly. All five patients developed a unique syndrome of severe infusion-related reactions, thrombocytopenia, rapid decrement in circulating tumor cell load, and mild electrolyte evidence of tumor lysis, and all required hospitalization. In addition, one patient developed ascites. These events resolved, and four patients were subsequently treated with rituximab without significant complications. CONCLUSION: Rituximab administration in patients who have a high number of tumor cells in the blood may have an increased likelihood of severe initial infusion-related reactions. These data also suggest that rituximab may have activity in a variety of other lymphoid neoplasms, such as chronic lymphocytic leukemia and B-cell prolymphocytic leukemia.

The effect of intravenous ketorolac given intraoperatively versus postoperatively on outcome from gynecologic abdominal surgery.

STUDY OBJECTIVES: To examine the effect of timing of an intravenous (i.v.) dose (intraoperative vs. postoperative) of ketorolac tromethamine on pain scores and overall outcome after total abdominal hysterectomy (TAH) and myomectomy. DESIGN: Prospective, randomized, placebo-controlled study. PATIENTS: 248 ASA physical status I and II adult female patients scheduled for elective hysterectomy or myomectomy. INTERVENTIONS: General anesthesia was administered that consisted of thiopental sodium for induction, enflurane or isoflurane in nitrous oxide-oxygen for maintenance, and small doses of fentanyl and midazolam. Patients were randomized into three groups to receive toradol/placebo on a dosing schedule of dose 1 given one-half hour prior to expected end of surgery, dose 2 given on awakening in the postanesthesia care unit, and doses 3, 4, and 5 given at 6, 12, and 18 hours, respectively, after dose 2; Group 1 patients received placebo (saline) for dose 1, ketorolac 60 mg i.v. for dose 2, and ketorolac 30 mg i.v. for doses 3, 4, and 5. Group 2 patients received ketorolac 60 mg i.v. for dose 1, placebo for dose 2, and ketorolac 30 mg i.v. for doses 3, 4, and 5. Group 3 patients received placebo for all doses. All patients were given i.v. morphine PCA postoperatively, and morphine usages, visual analog pain intensity (VAS) scores, as well as adverse events and median times to recovery milestones were recorded. MEASUREMENTS AND MAIN RESULTS: VAS scores (mean) before dose 2 were significantly lower in Group 2 than Group 1, as were at-rest evaluations at 15 minutes and one hour. Group 2 patients also had decreased morphine requirements as compared to placebo. Both ketorolac groups (Groups 1 and 2) had significantly higher values for patient and observer overall ratings, case of nursing care, and tolerability as compared to placebo (Group 3). There were no significant differences among groups in adverse events or median times to recovery milestones. CONCLUSIONS: Although it is possible to demonstrate an improvement in early postoperative pain scores with intraoperative ketorolac and better overall ratings of ketorolac both intraoperatively and postoperatively as compared with placebo, the lack of clinically significant differences in analgesic efficacy in the two active study groups indicates the need for a careful consideration by the clinician of the risks versus benefits involved in the administration of antiplatelet medication in the perioperative period.

Comparison of intravenous ketorolac, meperidine, and both (balanced analgesia) for renal colic.

STUDY OBJECTIVE: To compare the analgesic efficacy and safety of IV ketorolac, the only nonsteroidal antiinflammatory drug indicated for parenteral use in acute pain in the United States, with IV meperidine and with a combination of the two agents in renal colic. METHODS: We carried out a double-blind, randomized, multicenter clinical trial in the emergency departments of four urban tertiary care teaching hospitals. Our study subjects were 154 patients with suspected renal colic. Each subject received an initial IV dose of ketorolac 60 mg, meperidine 50 mg, or both supplemented as needed beyond 30 minutes with additional doses of meperidine. RESULTS: The main outcome measures were changes in pain-intensity and pain-relief scores, amount of supplemental meperidine required, end-of-study drug tolerability, and adverse events. Analyses of 106 subjects with confirmed renal colic indicated that ketorolac and the combination were significantly better than meperidine alone by all efficacy measures, including pain relief and time elapsed before the need for supplemental meperidine. By 30 minutes, 75% of the ketorolac group and 74% of the combination group had a 50% reduction in pain scores, compared with 23% of the meperidine group (P < .001). The ketorolac and combination groups did not differ significantly in any of the efficacy measures. CONCLUSION: IV ketorolac, alone or in combination with meperidine, was superior to IV meperidine alone in moderate and severe renal colic. Because many subjects in all three treatment groups received supplemental meperidine and because response to ketorolac alone cannot be predicted, clinicians may choose to initiate treatment with a ketorolac-meperidine combination.

A randomized, double-blind evaluation of ketorolac tromethamine for postoperative analgesia in ambulatory surgery patients.

BACKGROUND: Given the trend toward early discharge of patients after surgery and the inherent adverse effects of opioid analgesics, we compared a new nonsteroidal antiinflammatory drug, ketorolac tromethamine, given intravenously (iv) and then orally, with two commonly prescribed opioid analgesics in ambulatory patients for up to 1 week after surgery. METHODS: In this study incorporating a double-blind, multi-dose design, 221 patients who had moderate or severe pain after surgery were randomized to one of three treatment groups: group K30 received 30 mg iv ketorolac twice, then 10 mg iv every 30 min as required to control pain, up to six doses, followed by 10 mg oral ketorolac every 4-6 h; group F50 received 50 micrograms iv fentanyl at the same time intervals as in group K30, followed by 60 mg codeine plus 600 mg acetaminophen (C+A) orally every 4-6 h; and group F10 received the same combination as did group F50, but only 10 micrograms fentanyl per dose. RESULTS: Compared with 50 micrograms fentanyl iv, 30 mg iv ketorolac provided delayed but otherwise equivalent analgesic effects and was associated with similar side effects. Compared with C+A, 10 mg oral ketorolac was associated with a lower incidence of nausea and somnolence and earlier return of bowel function but not better pain relief, drug tolerability, quality of life, or psychologic well-being. CONCLUSIONS: Ketorolac, when used in an iv and then oral sequence, is a safe and effective analgesic in the ambulatory surgery setting. It has a slower onset than fentanyl, but causes fewer side effects than C+A.