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Implications of Recent Guideline Updates on the Management of Chemotherapy-induced Nausea and Vomiting Investigational Agents and Novel Formulations for CINV
• An intranasal granisetron spray is being evaluated in phase 1 clinical trials.1
Table 2 Emetogenic Risk Levels of Intravenous Chemotherapeutic Agents Based on NCCN Guidelines Riska Level
Agents
High risk (>90%)
AC combination (doxorubicin or epirubicin with cyclophosphamide) Carmustine (>250 mg/m2) Cisplatin (≥50 mg/m2)
Cyclophosphamide (>1500 mg/m2) Dacarbazine Mechlorethamine Streptozocin
Moderate risk (30%-90%)
Aldesleukin (>12 million-15 million IU/m2) Altretamine Amifostine (>300 mg/m2) Arsenic trioxide Azacitidine Bendamustine Busulfan Carboplatin Carmustine (≤250 mg/m2)
Cisplatin (<50 mg/m2) Clofarabine Cyclophosphamide (≤1500 mg/m2) Cytarabine (>200 mg/m2) Dactinomycin Daunorubicin Doxorubicin Epirubicin Mechlorethamine Streptozocin
Idarubicin Ifosfamide Interferon alpha (≥10 million IU/m2) Irinotecan Melphalan Methotrexate (250 - >1000 mg/m2) Oxaliplatin Temozolomide
Low risk (10%-30%)
Amifostine (≤300 mg) Aldesleukin (≤12 million IU/m2) Cytarabine (low dose) (100-200 mg/m2) Docetaxel Doxorubicin (liposomal) Etoposide 5-Fluorouracil
Paclitaxel Paclitaxel, albumin-bound Pemetrex Pentostatin Romidepsin Topotecan
Minimal risk (<10%)
Alemtuzumab Asparaginase Bevacizumab Bleomycin Bortezomib Cetuximab Cladribine (2-chlorodeoxyadenosine) Cytarabine (<100 mg/m2) Decitabine
Floxuridine Gemcitabine Interferon alpha (>5 - <10 million IU/m2) Ixabepilone Methotrexate (>50 - <250 mg/m2) Mitomycin Mitoxantrone Denileukin diftitox Dexrazoxane Fludarabine Gemtuzumab ozogamicin Interferon alpha (≤5 million IU/m2) Methotrexate (≤50 mg/m2) Nelarabine Panitumumab
• An oral ondansetron spray is being investigated in Europe.2 • A transdermal gel containing lorazepam, diphenhydramine, and haloperidol (referred to as ABH gel) is being evaluated in small pilot studies as a rescue therapy for breakthrough CINV.3 • In July 2010, the US Food and Drug Administration approved an ondansetron orally dissolving film strip, which is indicated for the prevention of CINV associated with HEC and MEC.4 This formulation is intended for patients who have difficulty swallowing, as well as those who cannot retain tablets in the gastrointestinal system long enough for them to fully dissolve. • A new ginger capsule to treat CINV is currently being evaluated in phase 2/3 clinical trials.5 References 1. Almac Discovery announces commencement of phase I trials of granisetron nasal spray. Medical News Today. www.medicalnewstoday.com/articles/ 174130.php. 2. BioAlliance acquired European rights for ondansetron oral spray to complement its franchise in cancer supportive care from NovaDel Pharma Inc. Medical News Today. www.medicalnewstoday.com/ articles/108166.php. 3. Bleicher J, Bhaskara A, Huyck T, et al. Lorazepam, diphenhydramine, and haloperidol transdermal gel for rescue from chemotherapy-induced nausea/vomiting; results of two pilot trials. J Support Oncol. 2008;6(1):27-32. 4. FDA approves Strativa Pharmaceuticals’ Zuplenz® (ondansetron) Oral Soluble Film. Medical News Today. www.medicalnewstoday.com/articles/193766. php. 5. Aphios announces presentation of phaseI/III clinical trial data on Zindol® for cancer chemotherapy induced nausea. Medical News Today. www.medical newstoday.com/articles/151593.php.
class of antiemetic drugs. These agents have been shown to be effective in preventing acute and delayed CINV associated with MEC and HEC when combined with a 5-HT3 RA and dexamethasone.1,14,20 The NK-1 RAs aprepitant and fosaprepitant dimeglumine (an IV version of aprepitant) work by selectively inhibiting the binding of substance P at the NK-1 receptor, thereby providing a different mechanism of action than other antiemetic agents. In a phase 3 randomized, controlled trial, aprepitant demonstrated a benefit when added to antiemetic regimens for 3 platinum agents—cisplatin, carboplatin, and oxaliplatin—with a lesser magnitude of benefit for the oxaliplatin regimen.21 Another study showed that without aprepitant administration, 20% of patients receiv-
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December 2010 I VOL 3, NO 8
Pegaspargase Rituximab Temsirolimus Trastuzumab Valrubicin Vinblastine Vincristine Vinorelbine
a
Risk = frequency of emesis in the absence of antiemetic prophylaxis. Source: Reference 1.
Table 3 Antiemetic Practice Guidelines: Web-based Resources Resource American Society of Clinical Oncology Multinational Association for Supportive Care in Cancer National Comprehensive Cancer Network
Website www.asco.org
Location in Website Practice & Guidelines (Supportive Care and Quality of Life)
www.mascc.org
Guidelines & Tools
www.nccn.org
Guidelines & Clinical Resources
Oncology Nursing Society
www.ons.org
Clinical Practice (Symptom Management)
ing carboplatin-containing regimens had moderate-to-severe delayed CINV.22 Furthermore, a retrospective cohort study of 3110 patients from 30 community-based oncology clinics showed that the type of chemotherapy regimen, younger age, and female gender were associated with a greater risk of CINV following HEC or MEC, whereas aprepitant use was associated with a decreased risk of CINV (16.2% for aprepitant users vs 21% for nonaprepitant users [P = .71]), suggesting that increased aprepitant use in HEC/ MEC may diminish CINV.23
Corticosteroids and other antiemetic agents First introduced more than 25 years ago, corticosteroids, including dexamethasone, continue to be used widely to prevent CINV.16 These drugs are effective as single agents in patients receiving chemotherapy with a low emetogenic risk.2 The addition of dexamethasone to antiemetic combinations containing 5HT3 RAs has also been shown to improve the efficacy of these regimens.1,2 Other antiemetic treatments that have been used for CINV include antihistamines, phenothiazines, substituted benza-
mides, butyrophenones, benzodiazepines, and cannabinoids.1 Olanzapine (an atypical antipsychotic agent) and gabapentin (GABA analogue/anticonvulsing agent) are currently being investigated for CINV.24,25 In a small phase 2 trial, olanzapine was shown to be effective for acute and delayed emesis in patients who received cyclophosphamide, doxorubicin, and/or cisplatin.1 Caution is recommended when using olanzapine in elderly patients, in accordance with the agent’s black box warning.1 Gabapentin is being studied in phase 3 studies to evaluate its efficacy in preventing CINV.26
www.TheOncologyPharmacist.com