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Updates in Symptom Management: Chemotherapy-Induced Nausea and Vomiting, and Oxaliplatin-Induced Neuropathy
Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update


Scope of the Problem


One of the most dreaded side effects of cancer treatment is chemotherapy-induced nausea and vomiting (Hesketh, 2009). Numerous advances have been made in combating this common symptom; however patients continue to rank CINV as distressing despite further understanding of the pathophysiology involved in this side effect and pharmacological improvements.. Practice guidelines are available to guide health care providers in the most optimal therapy choices. These evidence-based guidelines are written by practice experts; the most frequently used practice guidelines are the National Comprehensive Cancer Network (NCCN) guidelines (the currently available update is v.1.2012), the Multinational Association of Supportive Care in Cancer (MASCC) guidelines (updated in 2011), and the American Society of Clinical Oncology (ASCO) guidelines. ASCO has just published an update to their original Clinical Practice Guideline; this update incorporates a systematic review of the medical literature, using MEDLINE, the Cochrane Collaboration Library, and meeting materials from ASCO and MASCC (Basch et al. 2011). Thirty-seven trials met the prespecified inclusion and exclusion criteria for the review and the primary outcomes of interest were complete response and rates of any vomiting and nausea.


American Society of Clinical Oncology Clinical Practice Guideline Update on Antiemetics Highlights


  • Patients who receive highly emetic chemotherapy (HEC) regimens should receive the three-drug combination of a neurokinin 1 (NNK1) antagonist, 5-hydroxytryptamine-3 (5-Ht3) antagonist, and dexamethasone
  • The preferred 5-HT3 antagonist for moderately emetogenic chemotherapy (MEC) regimens is palonosetron, combined with a corticosteroid
  • Antiemetic treatment for patients receiving combination chemotherapy should be determined according to the agent with the greatest degree of emetic risk
  • Combination therapy including  dexamethasone and a 5-HT3 antagonist are recommended for patients undergoing high-dose chemotherapy
  • Patients treated with high emetic risk radiation therapy should receive a 5-HT3 antagonist before each fraction and a 5-day course of dexamethasone; moderate-risk radiation patients are also recommended to receive a 5-HT3 antagonist, with dexamethasone optional
  • Patients receiving combination chemoradiotherapy should receive antiemetic therapy dictated by the emetogenicity of the chemotherapy, unless the radiation therapy emetic risk is higher
The ASCO guideline update notes that the intravenous form of fosaprepitant can be used as a single day treatment for HEC as well as the three drug regimen of oral aprepitant, in combination with a 5-HT3 and dexamethasone. The Update Committee also notes that anthracycline and cyclophosphamide combinations are now classified as HEC, a change from the previous designation of MEC. The preferred designation of palonosetron in the MEC setting is new to this iteration of the guideline in comparison to the previous recommendation of 5-HT3. 


Duloxetine Improves Oxaliplatin-Induced Peripheral Neuropathy in Patients With Colorectal Cancer: An Open-Label Pilot Study


Scope of the Problem


Oxaliplatin is an integral part of the chemotherapy treatment options for patients with colorectal cancer (CRC). The dose-limiting side effect of this chemotherapy remains peripheral neuropathy and considerable research has been devoted to strategies to reduce this adverse event. The chronic form of oxaliplatin-induced peripheral neuropathy (OIPN) can lead to reduced quality of life and may require discontinuation of a potentially useful therapy for patients with CRC (Park, et al. 2011). A recently reported open-label pilot study by Yang and colleagues examines the use of duloxetine in the management of oxaliplatin-induced neuropathy (2011).


Study Facts


  • 39 patients with stage III or IV CRC and chronic OIPN enrolled in the trial
  • The patients received duloxetine; the dose was increased from 30 mg/day to 60 mg/day in one week with the patients’ pain intensity rated at baseline and 12 weeks after the administration of duloxetine
  • Severity of neuropathic pain was evaluated using the visual analog scale (VAS) and the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3 (NCI-CTCAE v. 3.0)
  • Nine of the patients (23.1%) discontinued duloxetine before the end of therapy due to adverse events thought to be related to the drug; out of the remaining 30 patients, 19 (63.3%) reported a VAS score improvement and nine of those patients (47.4%) demonstrated a grade improvement according to the NCI-CTCAE v.30 scale
  • Side effects leading to treatment discontinuation included dizziness, giddiness/nausea, somnolence, restlessness/insomnia and urinary hesitancy
  • Duloxetine did not interfere with renal or liver function and had no effect on chemotherapy treatments
  • The authors note that potential concerns with the use of duloxetine include drug-drug interactions.  Additionally, as a pilot trial, the number of patients studied was small; additional  research with a larger population should be conducted.

ManageCRC Commentary


Symptom management remains an essential part of caring for patients with cancer; the two reports referenced above discuss new information regarding management of symptoms associated with therapy for cancer. Clinical practice guidelines are important tools to assist the HCP in the decision-making process for optimal antiemetic therapy. Frequent updates in practice guidelines are essential to educate HCPs in the most current approaches to this often feared symptom. Additionally, patients with CRC usually receive oxaliplatin-based chemotherapy (MEC) for their disease; oncology nurses must stay abreast of the latest developments in practice guidelines, offering patients the most updated treatment options for CINV. Ongoing research should focus on improvements in management of CINV, with increasing focus on nausea as a particularly problematic component of this symptom.


The use of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor is novel in the treatment of OIPN. This agent has demonstrated significant activity in the management of diabetic peripheral neuropathic pain, and the trial reported by Yang et al. shows that duloxetine may be effective in OIPN as well (2011). Although this agent currently is not approved by the Food and Drug Administration (FDA) in the treatment of neuropathic pain, these results are promising and should form a basis for further research in the activity of duloxetine in OIPN.


References


Basch, E., Prestrud, A.A., Hesketh, P.J., Kris, M.G., Feyer, P.C., Somerfield, M.R.,…Lyman, G.H. (2011). Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of Clinical Oncology, [epub ahead of print], doi:10.1200/JCO.2010.34.4614  Link to abstract: http://www.asco.org/ASCOv2/Practice+%26+Guidelines/Guidelines/Clinical+Practice+Guidelines/Antiemetics%3A+American+Society+of+Clinical+Oncology+Clinical+Practice+Guideline+Update



Hesketh, P.J. (2009). Penny wise, dollar foolish approach to antiemetic use may compromise patient care. Journal of Oncology Practice, 5 (5), 221-222. doi:10.1200/JOP.091026    Link to free text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790656/pdf/jop221.pdf


Kris, M., Hesketh, P.J., Somerfield, M.R., Feyer, P., Clark-Snow, R., Koeller, J.M.,…Grunberg, S.M. (2006).  American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006. The Journal of Clinical Oncology, 24 (18), 2932-2947. doi:10.1200/JCO.2006.06.9591  Link to free text: http://jco.ascopubs.org/content/24/18/2932.full.pdf+html


Multinational Association of Supportive Care in Cancer (MASCC). MASCC/ESMO Antiemetic Guideline 2011. Link to guideline: http://data.memberclicks.com/site/mascc/MASCC_Guidelines_English_2011.pdf


National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) Antiemesis v 1.2012. Retrieved from: http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf 


Park, S.B., Lin, C.S., Krishnan, A.V., Goldstein, D., Friedlander, M.L., & Kiernan, M.C. (2011). Long-term neuropathy after oxaliplatin treatment: challenging the dictum of reversibility. Oncologist, 16 (5), 708-716. doi: 10.1634/theoncologist.2010-0248  Link to abstract: http://www.ncbi.nlm.nih.gov/pubmed/21478275


Yang, Y.H., Lin, J.K., Chen, W.S., Lin, T.C., Yang, S.H., Jiang, J.K.,…Teng, H.W. (2011). Duloxetine improves oxaliplatin-induced neuropathy in patients with colorectal cancer: an open-label pilot study. Supportive Care in Cancer, [epub ahead of print], doi:10.1007/s00520-011-1237-2   Link to abstract: http://www.ncbi.nlm.nih.gov/pubmed/21814779


Article Created On : 10/12/2011 10:34:35 AM             Article Updated On : 10/12/2011 10:34:35 AM