Matulonis_subbed.qxp 13/7/09 10:55 Page 12
Supportive Oncology
Table 2: Common Emetogenic Regimens
Highly Emetogenic Agents
Altretamine, carmustine, cisplatin, cyclophosphamide >1,500mg/m
2
, dacarbazine (DTIC), dactinomycin, ifosfamide (Ifex) >1.5g/mg/m
2
, lomustine (CCNU), mechlorethamine
(nitrogen mustard), methotrexate >1,000mg/m
2
, pentostatin, procarbazine, streptozocin
Combinations: ABVD, AC, AIM, BEP, CAF, CAV-IE, ChIVPP, CHOP/R-CHOP, DHAP, ECF, gemcitabine/cisplatin, hyper-CVAD/MTX/cytarabine, ICE/R-ICE, TPF
Moderately Emetogenic Agents
Aldesleukin >12–15 million units/m
2
, amifostine >300mg/m
2
, azacitidine, busulfan >4mg/g, carboplatin, carmustine <250mg/m
2
, cyclophosphamide <1,500mg/m
2
,
cytarabine (Ara C) >1,000mg/m
2
, dactinomycin, daunorubicin, doxorubicin, epirubicin, etoposide (oral), idarubicin, ifosfamide <1.5g/m
2
, imatinib (oral), irinotecan (CPT-11),
ixabepilone, lomustine, melphalan, methotrexate 250–1,000mg/m
2
, oxaliplatin, temozolamide, vinorelbine (oral)
Combinations: Carboplatin/5-FU/LCV, CMF, CVP, docetaxol/carboplatin, EC, gemcitabine/carboplatin, gemcitabine/oxaliplatin, oxaliplatin/5-FU/LCV, irinotecan/5-FU/LCV,
paclitaxel/carboplatin
Low to Minimally Emetogenic Agents
Alemtuzumab, amifostine <300mg/m
2
, asparaginase, bevacizumab, bexarotene, bleomycin, bortezomib, busulfan, capcitabine, cetuximab, chlorambucil, cladribine (2-CDA),
cytarabine <100mg/m
2
, dasatinib, decitabine, dexrazoxane, docetaxol, doxorubicin liposomal, etoposide (VP-16), erlotinib, floxuridine, fludarabine, 5-fluorouracil, gefitinib,
gemcitabine, gemtuzumab, hydroxyurea, lapatinib, lenalidomide, mercaptopurine, methotrexate <250mg/m
2
, mitomycin C, mitoxantrone, nelarabine, paclitaxel, paclitaxel-
albumin, panitumumab, pemetrexed, pentostatin, rituximab, sorafenib, sunitinib, temsirolimus, thalidomide, thioguanine, topotecan, trastuzumab, vinblastine/vincristine,
vinorelbine, vorinostat
delayed emesis.
30
5-HT3 antagonists have been identified to prevent corticosteroids. Study of the addition of aprepitant to standard
50–70% of acute CINV.
31
This class includes dolasetron, granisetron, ondansetron and dexamethasone in highly emetogenic cisplatin therapy
ondansetron, palonosetron, and tropisetron. None of the 5-HT3 showed superior control to the standard therapy, with complete
antagonists is identified as preferentially recommended by MASCC, protection of 82.8 versus 68.4%.
38
If given in combination with
NCCN, or ASCO guidelines. aprepitant, the dose of the steroid should be decreased as
dexamethasone is a sensitive substrate for the cytochrome P450 (CYP
Palonosetron, the newest 5-HT3 antagonist, was introduced in 1993. It P450) 3A4 enzyme. Corticosteroids may cause hyperglycemia in patients
has a higher binding activity, estimated to be 100-fold stronger than with diabetes and may cause changes in mental status.
other 5-HT3 antagonists, and a longer half-life of approximately 40
hours.
32
Palonosetron is available in intravenous preparations only. It is Substance P Inhibitors
approved by the US Food and Drug Agency (FDA) for preventing acute Aprepitant is an oral regimen for the prevention of acute and delayed
CINV associated with moderately and highly emetogenic chemotherapy nausea and vomiting that works by binding to the protachykinin-1
and for the prevention of delayed CINV associated with moderately receptor. Protachykinin-1, a mediator of pain, inflammation, nausea, and
emetogenic chemotherapy. A randomized double-blind trial of vomiting, cannot bind to aprepitant-occupied receptors.
39
Other
palonosetron versus ondansetron showed higher efficacy rates for protachykinin-1 receptor antagonists include L-758,298, vofopitant,
palonosetron in controlling both acute (81 versus 69%) and delayed (48 CP-122,721, and CJ-11,974; however, aprepitant is the only clinically
versus 31%) emesis.
33
In a trial against dolansetron, palonosetron was available drug. Aprepitant is an oral regimen that is recommended for a
equivalent in preventing acute CINV and superior in preventing delayed three-day course, and has been shown to control cisplatin CINV in the
CINV after moderately emetogenic chemotherapy.
32
Trials comparing acute and delayed phase in two randomized, placebo-controlled phase
traditional 5-HT3 antagonists with palonosetron have been criticized III studies.
40,41
These trials studied 1,099 patients who received 70mg/m
2
for not routinely including corticosteroids with traditional 5-HT3s for cisplatin and who were randomized to receive ondansetron and oral
prevention of delayed CINV.
34
Common side effects of 5-HT3 dexamethasone followed by oral dexamethasone twice daily on
antagonists include dizziness, headache, and diarrhea or constipation. days two to four after chemotherapy versus aprepitant before
They are not associated with sedation or extrapyramidal symptoms chemotherapy followed by aprepitant and dexamethasone daily on days
(EPS). 5-HT3 may also cause asymptomatic electrocardiogram changes two and three followed by dexamethasone on day four. The aprepitant
including prolonged PT and QTc intervals. groups performed better in controlling overall emetic response: 63 and
73% versus 43 and 52% for the control groups.
Corticosteroids
Methylprednisone (MP) and dexamethasone are recommended for Data exist that support the notion that aprepitant is effective in
prevention of acute CINV for low and moderately emetogenic controlling nausea and vomiting from moderately emetogenic
chemotherapy.
35
The mechanism underlying corticosteroid efficacy is chemotherapy.
42
MASCC and NCCN guidelines recommend aprepitant
unknown; however, it is hypothesized that MP decreases cisplatin- as an additional component to corticosteroids and 5HT3 antagonists
induced 5-HT release from peripheral blood mononuclear cells.
36
In early for prophylaxis against CINV of highly emetogenic chemotherapies.
18
studies, dexamethasone was shown to be superior to metoclopramide
in patients receiving non-platinum-based regimens.
37
Previously, 5HT3 Recently, fosaprepitant, an intravenous neurokinin-1 receptor
antagonists—metoclopramide and dexamethasone combinations— antagonist, has been submitted to the FDA as a parenteral alternative
were considered standard of care. Multiple studies with 5-HT3 to aprepitant.
43
Dizziness, constipation or diarrhea, headache, and
antagonists have demonstrated improved control with the addition of weakness are side effects of aprepitant. There exists potential for
12 US ONCOLOGY
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100