eppie Posted December 23, 2005 Share Posted December 23, 2005 Albumin-Bound Paclitaxel, Clofarabine, and Erlotinib Expand Therapeutic Options for Cancer Patients: Presented at ONS By Bonnie Darves PHOENIX, AZ -- November 14, 2005 -- The past 2 years have been banner ones for the development of new cancer therapies, marked by the emergence of both novel agents and alternate formulations of existing drugs. In their drug update here at the Oncology Nursing Society 6th Annual Institutes of Learning (ONS), on November 11th, Debbie Sisson, RPh, MS, pharmacist, St. Mary's Medical Center, Duluth, Minnesota, and Deb Thompson, RN, BA, oncology clinical research nurse, Duluth Clinic Cancer Center, Duluth, Minnesota, discussed the upsides and potential downsides of the new therapies. Abraxane Nanoparticle Albumin-Bound Paclitaxel One the most newsworthy developments is the availability of the nanoparticle albumin-bound paclitaxel -- Abraxane -- for treatment of patients with refractory metastatic breast cancer. Calling it "the most exciting drug we're talking about today," Ms. Sisson explained that Abraxane represents "a new way to deliver medication." The formulation actually combines active ingredient of taxol with the natural protein albumin, using nanoparticle technology that allows for absorption of the drug directly in the tumor. "It's a whole new system of delivery that offers new [treatment] options for patients," she said, adding that the solvent-free nanoparticle approach likely will be used for other agents as well. Abraxane is also being considered for use in ovarian, lung, and head and neck cancers, Ms. Sisson noted, and is being investigated as a first-line treatment for metastatic breast cancer. In recent trials of the drug in patients who relapsed after combination therapy, response rates were up to 85% compared with Taxol, and time to tumor progression was significantly longer. In addition to its efficacy, Abraxane's chief benefits are that its targeted delivery is less damaging to normal tissue, and its toxicity profile is far better than other agents, because it does not contain the Cremophor-EL and ethanol used in traditional formulations. In particular, Ms. Sisson noted, the drug reduces the neuropathy associated with Taxol. Ms. Thompson added a third benefit of Abraxane for patients and nurses -- a short infusion time of 30 minutes. Dosing is 260 mg/m2 every 3 weeks, Ms. Thompson said, and nurses should keep in mind that its dosing is "very different than Taxol and the 2 aren't interchangeable." Abraxane: Monitoring and Management Although dose reductions can be made -- to 200 mg/m2 and 180 mg/m2 -- few patients need dose reductions because Abraxane is associated with low toxicity rates, she added. "Many patients seem to tolerate it very well." The chief adverse effects are nausea and vomiting, which can be managed with standard antiemetics. Peripheral neuropathy is an issue with the drug, and affects approximately 10% of patients, but it tends to be both shorter lived and more readily managed than the neuropathy associated with other similar cancer therapies. "It usually resolves on its own" in less than a week, Ms. Thompson said. She added that toxicities appear to be no worse with older patients than with younger ones, in her experience. Myalgia and arthralgia are common adverse effects of Abraxane "and should be treated aggressively," Ms. Thompson said, possibly by giving patients Tylenol (acetaminophen) at the time the drug is given. Although the drug is relatively easy to administer, nurses should be prepared for its foamy appearance and the possibility that it will "cake up" before settling. As such, she advised to let drug "sit" for 5 minutes before administration, Ms. Thompson said. On the plus side, premedication with antihistamines and steroids is not needed, and administration does not require special tubing or filters. Clofarabine (Clolar) Recently approved to treat refractory pediatric acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML), the second-generation nucleoside clofarabine (Clolar) has promise "to take on the best properties of others in its class" by employing 2 mechanisms of action. The drug inhibits both ribonucleotide and DNA, and also acts directly on the mitochondria, thereby "interrupting the metabolism of cancer cells," Ms. Thompson said. Investigators have found that the drug may be more beneficial if it is used after the first relapse, rather than subsequent ones. Clofarabine is also being investigated for use in solid tumors and other hematologic malignancies such as non-Hodgkin's lymphoma. While the drug has great promise, Ms. Sisson cautioned that potentially renotoxic medications (as well as hepatotoxic medications) should be avoided within 5 days of its administration because it is primarily excreted by the kidneys. Dosing in pediatric patients is 52 mg/m2 daily for 5 consecutive days, every 3 to 6 weeks. Ms. Sisson urged nurses who administer the drug to remember to take height and weight measurements before each administration, and to closely monitor hepatic and renal function, as well as respiratory status. Clofarabine: Monitoring and Management One of the most serious adverse effects of clofarabine is hypotension, which warrants discontinuing the drug if it develops during the 5-day administration period, Ms. Thompson noted. If the episodes are transient, the drug may be restarted, she added. Dehydration is a potential problem, she added, which means the drug should be administered only in the inpatient setting. If hyperuricemia is expected to develop, allopurinol should be used. The most common adverse effects are reversible hepatotoxicity, nausea, vomiting, and diarrhea. Some patients also complain of headache and infusion-related flushing. Erlotinib (Tarceva) This targeted oral drug, approved for use in non-small-cell lung cancer (NSCLC), received FDA approval (in combination with gemcitabine) in early November 2005 for treatment of pancreatic cancer. Erlotinib works by inhibiting cancer cell protein epithelial growth factor (EGF), "helping to spur cells to divide," Ms. Sisson said, likening the drug's action mechanism to that of Iressa (gefitinib) -- which was approved at the same time but recently received a use-limiting label change. The drug, because of its mechanism, also has potential for breast, prostate, renal, and hepatic tumors, and other "cancers that don't have a very good prognosis," Ms. Sisson said. In recent trials of NSCLC, patients on erlotinib lived 2 months longer than those on placebo. "At first glance, that might not seem significant, but patients with this [cancer] have a very poor prognosis, so 2 months is significant," she said. Patients in this trial also experienced substantial relief from the common symptoms of coughing, pain, and breathing difficulty. "Tarceva appears to hold those symptoms at bay for a while," she said. The drug also is being investigated in patients with metastatic breast cancer, Ms. Thompson said. Recommended dosing is 150 mg daily between meals, and daily dosing should not be doubled if patients miss a dose, Ms. Sisson said. She cautioned that because of the drug's potentially problematic interaction profile, patients should be urged to disclose all medications they are taking, including oral contraceptives and antihistamines, and that information should be provided to the pharmacists. Erlotinib Monitoring and Management The chief adverse effects are skin-related, including a potentially severe acneiform-type of rash that affects up to 75% of patients, Ms. Thompson noted. Because the rash is commonly located on the face and arms and can be severe and painful, some patients request dose reduction or even decide to discontinue the drug, she added. "Patients really should be told to expect these skin effects, and to report them to the nurse as soon as they occur so that they can be treated," she said, adding that the rash tends to be more severe in patients with a history of acne and is worsened by exposure to heat, humidity, or sunlight. The rash subsides relatively quickly when the drug is discontinued. The other potentially dose-limiting effect is diarrhea, which affects approximately half of patients. Rare cases of interstitial lung disease have also been reported, and can be difficult to detect in patients with lung cancer. Ms. Thompson noted that this adverse effect is usually accompanied by fever. [Presentation title: New Drug Update.] Quote Link to comment Share on other sites More sharing options...
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