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Treatment Advances in Colorectal Cancer Often Accompanied by Toxicity Management Challenges: Presented at ONS

By Bonnie Darves

PHOENIX, AZ -- November 17, 2005 -- Patients with advanced or recurrent colorectal cancer (CRC) have many more treatment options that they did a decade ago, but the increased chemotherapy alternatives and their toxicities may present challenges for oncology nurses who manage these patients.

Pamela Hallquist Viale, RN, MS, AOCNP, assistant clinical professor, University of California, San Francisco, and oncology nurse practitioner, Camino Medical Group, Sunnyvale, California, discussed the advantages and disadvantages of working with patients with stage III or IV CRC.

The presentation was part of an ancillary session that took place during the annual clinical meeting of the Oncology Nursing Society 6^th Annual Institute of Learning (ONS).

On the upside, caring for patients with more advanced disease -- 30% to 40% of patients present at stage III -- is less gloomy than it was a decade ago, Ms. Viale said, because there are many more treatment options.

"Those of us who have been in oncology for a while have been able to see the change for these patients," she said. "We have many more options to offer them, and outcomes are much better."

She cited the recent emergence of drugs such as oxaliplatin, capecitabine, cetuximab, bevacizumab, and irinotecan. As monotherapy or in combination, these drugs have become viable alternatives to 5-fluorouracil (5-FU) plus leukovorin combination therapy, which became the standard of care in the late 1990s.

These developments made caring for this patient population more complex for nurses, because patients who receive aggressive chemotherapy, sometimes in combination with radiation, will experience more toxicities.

Ms. Viale provided an overview of the primary toxicities associated with the new drugs and proposed a range of management strategies oncology nurses might employ.

Oxaliplatin
Peripheral neuropathy and neutropenia are the primary toxicities of this drug, whether used in combination with 5-FU or other agents. As with other platinum drugs, hypersensitivity is also an issue and is a primarily delayed symptom, appearing after the second administration, Ms. Viale noted.

The neurotoxic effects of oxaliplatin -- ranging from paresthesias, dysesthesias and hypoesthesias to proprioception -- can be acute and persistent (up to 14 days), and may be exacerbated by exposure to cold.

Rare cases of acute pharyngolaryngeal dysesthesia have been cited, she said. Because that can be particularly frightening to patients, Ms. Viale advised attendees to educate their patients ahead of time that it might happen and instruct them to drink warm liquids if it occurs.

Management of oxaliplatin toxicities requires a proactive approach, Ms. Viale noted, and cited reports showing that 1 g each of calcium and magnesium chloride over 15 minutes before and after oxaliplatin administration can reduce both the incidence and severity of neuropathy.

Irinotecan
The most frequent toxicities with this drug are neutropenia and diarrhea. The latter can be acute or delayed, and is very common, occurring in between 50% and 80% of patients. Ms. Viale recommended using atropine for acute diarrhea and oral loperimide 4 mg initially and 2 mg every 4 hours when occurrence is delayed.

She noted that complicated cases might require hospitalization. If diarrhea persists for more than 24 hours, patients should be given oral fluoroquinolone. "This is a much more aggressive management approach now, and it's needed to stay on top of the diarrhea," she said.

Adherence to treatment can be a challenge with elderly patients, Ms. Viale noted, because some don't understand the importance of continuing the antidiarrheal therapy.

Cetuximab
The chief toxicities with cetuximab are infusion reactions and potentially severe acneiform rash. Infusion reactions are common, so patients should be premedicated with IV diphenhydramine in a 50-mg dose. A recent labeling change addresses this adverse effect, Ms. Viale noted, by recommending a postadministration observation period of 1 hour.

Rash, in some cases with a very pustular appearance, has emerged as the major toxicity with cetuximab and affects up to 80% of patients. This effect is best managed with lotions, antihistamines, and antibiotics, Ms. Viale advised, and cautioned against using acne drugs and drying medications of any type.

Rare pulmonary problems, specifically interstitial lung disease, have been reported with cetuximab, with an incidence of less than 0.5%. "It's rare, but if your patients complain of shortness of breath, you certainly want to evaluate that," she noted.

Capecitabine
Besides the neutropenia that is common with many cancer drugs, the primary toxicity of capecitabine is hand-foot syndrome (HFS). Characterized by drying and swelling of palms and the soles of the feet, the condition may be severe enough to warrant pain control, Ms. Viale said. She advised nurses to remember to check patients' feet at each visit, and to recommend topical emollients at the first sign of HFS.

"Patients should also be told to avoid friction and pressure on their hands and feet," she added, as well as contact with hot water or very warm objects. Elevation of the extremities may help alleviate symptoms, but severe HFS may warrant dose reduction or drug discontinuation.

Other toxicities of capecitabine include nausea, diarrhea, mucositis, and hyperbilirubinemia.

Bevacizumab
One of the chief adverse effects of bevacizumab is hypertension, which can be managed readily with standard antihypertensive medications. Potentially more problematic is bleeding, which frequently appears as mild epistaxis, Ms. Viale explained, but some patients have required hospitalization.

In preparing for the start of chemotherapy, the drug's antiangiogenic effects -- which may delay wound healing -- can become a problem. As such, bevacizumab administration should not begin before 28 days postsurgery.

Other rare toxicities of bevacizumab include gastrointestinal perforation and arterial thrombosis. The latter effect prompted a recent relabeling of the drug, Ms. Viale noted, which advises health care providers to monitor patients for signs of cerebral or myocardial infarction, transient ischemic attack or angina.

"The data show that the older the patients are, the more their risk increased for these problems," Ms. Viale said.

The session was supported by Sanofi-Synthelabo Inc.


[Presentation title: Management of Advanced and Recurrent Colorectal Cancer.]

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