New colorectal cancer drug approved in record time

September 2, 2002

The recent approval of oxaliplatin (Eloxatin, Sanofi-Synthelabo) by the FDA provides a treatment option for patients who previously did not have any alternatives except symptom-directed care. The Agency approved oxaliplatin, for use in combination with 5-fluorouracil (5-FU) and leucovorin (LV), for the treatment of patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed during or within 6 months of completion of first-line therapy with the combination of bolus 5-FU/LV and irinotecan (Camptosar, Pharmacia & Upjohn).

 

Rx CARE

New colorectal cancer drug approved in record time

The recent approval of ox- aliplatin (Eloxatin, Sanofi- Synthelabo) by the Food & Drug Administration provides a new treatment option for cancer patients. The agency approved oxaliplatin for use, in combination with 5-fluorouracil (5-FU) and leucovorin (LV), for the treatment of patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed during or within six months of completion of first-line therapy with the combination of bolus 5-FU/LV and irinotecan (Camptosar, Pharmacia).

Prior to the approval, symptom-directed care was the only option remaining to these patients, said Mace Rothenberg, M.D., Ingram Associate Professor of Cancer Research, Vanderbilt-Ingram Cancer Center, Nashville, and LaMar McGinnis, M.D., Senior Medical Consultant, American Cancer Society. The approval was completed in seven weeks, the fastest review to date for an oncology drug, according to the FDA.

Oxaliplatin is contraindicated in those with a known hypersensitivity to platinum compounds, Rothenberg and McGinnis said. (The package insert features a black box warning that anaphylactic reactions to oxaliplatin have been reported.)

The drug is classified as a pregnancy category D and should not be used in women who are pregnant or lactating. It is safe to use in older persons. The PI warns that the combination of oxaliplatin and 5-FU/LV should be used with caution in those with preexisting renal impairment, because the primary route of elimination is through the kidneys.

Oxaliplatin therapy is associated with two different types of neuropathy, Rothenberg cautioned. The first is an acute, reversible neuropathy that occurs anywhere from several hours to one to three days after treatment with oxaliplatin—usually resolving in fewer than 14 days. Symptoms are exacerbated by cold objects or cold temperatures. Subjective dysphagia and dyspnea (although patients are still actual- ly breathing on their own) are sometimes characteristic of this type of neuropathy, Rothenberg added.

The second type of neuropathy is related to the duration of oxaliplatin therapy and the total cumulative drug dose, Rothenberg said. As stated in the PI, this type of neuropathy is characterized by paresthesias, dysesthesias, and hypoesthesias and may include deficits in proprioception. He explained that this kind of neuropathy is not cold-sensitive, and symptoms can persist for more than 14 days.

McGinnis and Rothenberg described gastrointestinal side effects that are common to many chemotherapy drugs, including nausea, vomiting, and diarrhea. Adverse hematologic effects, such as anemia, leukopenia, neutropenia, and thrombocytopenia, occurred in 5% or more of patients in clinical trials. McGinnis mentioned that some alopecia can also occur. Standard laboratory monitoring of white blood cell count with differential, platelet count, hemoglobin, and blood chemistries is recommended before each cycle of oxaliplatin, the physicians emphasized.

The recommended dosage of oxaliplatin is 85 mg/m2—given as an IV infusion over two hours. On the first day of the treatment cycle, it can be given at the same time as 200 mg/m2 of LV, which is also administered as an IV infusion over two hours. The oxaliplatin and the leucovorin are followed by 400 mg/m2 of 5-FU, given as an IV bolus over two to four minutes. This is followed by 600 mg/m2 of 5-FU given as a continuous IV infusion over 22 hours. On the second day of treatment, 200 mg/m2 of LV—given as an IV infusion over two hours—is followed by 400 mg/m2 of 5-FU, given as an IV bolus over two to four minutes. This is followed by 600 mg/m2 of 5-FU, given as a continuous IV infusion over 22 hours. The cycle should be repeated every two weeks.

McGinnis feels encouraged by the rapid approval of oxaliplatin and the hope that it offers cancer patients. He expressed the hope that this approval will be a model for future FDA reviews.

Charlotte LoBuono

TIPS TO REMEMBER: Eloxatin

  • Eloxatin and leucovorin can be administered simultaneously in separate bags using a Y-line.

  • Prolonging the infusion time from two hours to six hours or administering anxiolytic medication such as benzodiazepines may prevent subjective dyspnea or dysphagia altogether or provide relief from the anxiety that these unpleasant sensations cause.

  • Hypersensitivity reactions can occur during any cycle of chemotherapy. They can sometimes occur after the seventh or eighth cycle, even if the patient has not previously demonstrated hypersensitivity.



Charlotte LoBuono. New colorectal cancer drug approved in record time.

Drug Topics

2002;17:12.