Is it safe to administer paclitaxel in one-hour infusion?
What can you do in one hour? Drive to work, make a meal? How about administering a paclitaxel infusion? That's exactly what healthcare providers can do in an hour at the outpatient oncology clinic at University of Massachusetts Memorial Medical Center.
When first approved, paclitaxel, one of the most active antineoplastics against a variety of tumors, was intended to be administered over 24 hours along with premedications in order to avoid hypersensitivity reactions. The length of infusion was first questioned in a 1994 study, in which a group of researchers addressed the dose-response relationship of paclitaxel and the safety of a short infusion given over three hours. Not only were the 24-hour and three-hour paclitaxel infusions similar in efficacy, the three-hour infusion was actually associated with a lower incidence of neutropenia than the 24-hour infusion.
Since then, evidence has accumulated in favor of an even shorter, one-hour paclitaxel infusion, as part of an outpatient weekly or every-three-weeks regimen. And why not push the envelope? Contrary to the belief that one-hour infusions would have a greater propensity to cause hypersensitivity reactions, published clinical trials demonstrate that a similar incidence of about 3% is seen in one- and three-hour paclitaxel infusions. Overall, the rate of hematological toxicity and neurotoxicity seen with one-hour infusions does not appear to be different from that observed with three-hour infusions.
Moreover, one-hour infusions of paclitaxel can prove be extremely advantageous in the outpatient setting by enhancing the patient's quality of life and reducing administration costs. The shorter time may also increase the total number of patients who can be treated daily in the outpatient setting. "Despite the mounting evidence, most clinicians continued to administer paclitaxel over three hours," said David C. Gammon, R.Ph., an oncology pharmacist at UMass Memorial Medical Center.
The disparity in practice prompted Gammon to perform a study to assess the safety of a one-hour paclitaxel infusion in various types of malignancies. During the two-year trial period, 33 patients received one-hour infusions of paclitaxel at a mean dose of 175 mg/m2. All patients received premedications 30 minutes prior to the infusion. The one-hour infusion was well tolerated, with the frequency of hypersensitive reactions at 3%. And "there was a potential for total cost savings of more than $10,000 during the two-year period," he declared. In addition to the financial benefits, patient satisfaction was enhanced.
Henry Fernandez, R.Ph., at Newark (N.J.) Beth Israel Medical Center, agreed. "Using one-hour infusions would not only have a positive impact on patients' quality of life but would also free up healthcare providers to treat other patients," he said. He added that he welcomes additional studies evaluating the safety of shorter paclitaxel infusions. And they certainly exist.
Several trials in patients with non-small-cell lung cancer (NSCLC) have demonstrated the efficacy and safety of high-dose paclitaxel, administered over one hour. In one large multicenter study, 155 outpatients with advanced NSCLC were treated with paclitaxel 225 mg/m2 via a one-hour infusion. Leukopenia and cumulative peripheral neuropathy did occur, but the complications rarely affected the course of therapy or were severe. Clinical studies have also evaluated a one-hour infusion of high-dose paclitaxel in patients with other tumor types.
Although the argument in favor of shorter paclitaxel infusions appears to be persuasive, it's not definitive. "Clinicians at most, if not all, institutions continue to administer paclitaxel over three hours for nonweekly regimens and for the treatment of nonlung tumors," declared Gammon.
Maya Shah, M.D., an oncologist at Newark Beth Israel, currently prefers this conservative approach. "I feel more comfortable giving high doses of paclitaxel over three hours, because longer-term, and more controlled studies using one-hour infusions are still warranted in certain types of malignancies," Shah stated.
So what administration recommendations for one-hour paclitaxel infusions can you make to your clinicians? In a 1999 article, researchers indicated that the incidence of hypersensitivity reactions associated with one-hour paclitaxel infusions is relatively low. However, they suggested using premedications to prevent such a reaction.
All patients should be screened in order to identify individuals who are unable to tolerate excess fluid load and/or rare cardiac effects of paclitaxel. Patients with congestive heart failure, a second-degree or higher heart block, or those with a myocardial infarction within the past six months should not receive paclitaxel via a one-hour infusion.