New Directions in the Management of Chemotherapy-Induced Na - PowerPoint Presentation

Slide1

New Directions in the Management of Chemotherapy-Induced Nausea and Vomiting

David S. Ettinger, MD

Alex Grass Professor of Oncology

Sidney Kimmel Comprehensive Cancer Center

at

Johns HopkinsSlide2

Disclosure of Conflicts of InterestDavid S. Ettinger, MD, discloses that he has served as an advisor/consultant for Gilead, Roche/Genentech, Boehringer Ingelheim, Biodesix, Lilly, and Helsinn Therapeutics.Slide3

Learning ObjectivesDescribe the pathophysiology of chemotherapy-induced nausea and vomiting (CINV)Assess the risk for nausea and vomiting in cancer patients scheduled to receive chemotherapyDifferentiate antiemetic strategies for delayed, breakthrough, and refractory nausea and vomitingSlide4

Physiology of CINVWickham, 2012.Slide5

Neurotransmitters in EmesisHesketh et al, 2003; Wickham, 2012.Slide6

Serotonin and the 5-HT3 Receptor PathwayPathway first recognized with high-dose metoclopramideIntroduction of 5-hydroxytryptamine (5-HT3) receptor antagonists offered an improved treatment optionEffective in acute vomiting; variable efficacy for delayed eventsPrimary mechanism of action appears to be peripheralMiner & Sanger, 1986; Andrews et al, 1998; Hesketh et al, 2003; Wickham, 2012.Slide7

Substance P and the NK1 Receptor PathwaySubstance P relays noxious sensory information to the brain (ie, modulates nociception)High density of substance P/neurokinin-1 (NK1) receptors located in brain regions is implicated in the emetic reflexPrimary mechanism of NK1 receptor blockade action appears to be centralEffective for both acute and delayed eventsAugments antiemetic activity of a 5-HT3 receptor antagonist and a corticosteroidDeVane, 2001; Hargreaves, 2002; Hesketh et al, 2003; Hesketh, 2001; Tattersall et al, 1996; Wickham, 2012.Slide8

Identical surveys conducted before and after the availability of 5-HT3 antagonists showedlittle change in patient perceptions

1983

1995

Rank

Symptoms

Rank

Symptoms

1

Vomiting

1

Nausea

2

Nausea

2

Loss of hair

3

Loss of hair

3

Vomiting

Side Effects Most Distressing to Patients Receiving Emetogenic Chemotherapy

de Boer-Dennert et al, 1997.Slide9

AcuteOccurs and resolves within 24 hours of chemotherapyGenerally peaks within 5 to 6 hoursDelayed

Occurs 1 to 6 days after chemotherapy

Common with administration of cisplatin, carboplatin, cyclophosphamide, and doxorubicin

Breakthrough

Occurs despite prophylactic treatment

Requires rescue therapy

Can be acute or delayed

Refractory

Occurs during chemotherapy cycle after prophylaxis and/or rescue therapy has failed in earlier cycles

Classification of CINV

National Comprehensive Cancer Network (NCCN), 2014.Slide10

Characterizing NauseaLess understood at neurochemical level than vomitingResults of direct treatment not as effective as treating vomitingImpact of nausea on quality of life (QOL) often overlookedGrunberg, 2012.Slide11

Characterizing Nausea (cont.)Vomiting an objective eventNausea a subjective symptomNausea commonly suffered in silence (difficult to grade)Grunberg, 2012.Slide12

Impact of Nausea on QOLNausea has more of a deleterious effect on QOL and sense of well-being than emesisPatients rate severe nausea worse for QOL than vomiting with or without nausea Börjeson et al, 2002; Bloechl-Daum et al, 2006; Sun et al, 2005; Grunberg, 2012.Slide13

The Importance of Treating NauseaNausea duration may result in even greater distress and altered QOL than severity of nauseaReduction of nausea rather than emesis has been shown to guide patient preference in antiemetic treatmentGrunberg, 2012.Slide14

CINV Risk FactorsTreatment-related risk factorsHigh emetogenicity of chemotherapy drugsHigh drug dosePatient-related risk factorsYounger ageFemale genderNo/minimal history of alcohol useSusceptibility to motion sicknessPoor control with prior chemotherapyAnxiety

NCCN, 2014.Slide15

CINV Risk Factors (cont.)Medical procedures such as surgery and radiationMedications such as digitalis derivatives, opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and antibioticsUremiaHypercalcemiaHepatic dysfunctionIncreased intracranial pressureGastrointestinal abnormalities: obstruction, ascites, hepatomegaly, paraneoplastic syndrome, gastroparesis, gastric outlet syndrome

NCCN, 2014. Slide16

Prevalence of CINV:

Highly Emetogenic Chemotherapy

Warr

et al, 2005; Hesketh et al, 2003.

(HEC)Slide17

Incidence of CINV with Common HEC Regimens

Jones et al, 2006; Neijt et al, 2000; Piccart et al, 2003; Manegold et al, 2000. Slide18

CINV: Predictability and PreventabilityCINV is a common, often predictable, and often preventable adverse reaction to chemotherapyConsider using preventive measures for CINV with cycle 1 of chemotherapyCINV negatively affects patients’ overall chemotherapy experiencePreventing CINV on first exposure to chemotherapy can reduce the risk for developing anticipatory CINV in subsequent cycles

Lau et al, 2004;

Basch

et al, 2011;

Osoba

, Zee,

Warr

, et al, 1997; Aapro et al, 2005;

Fernández

-Ortega et al, 2012.Slide19

Risk Factors for CINV: Chemotherapy-SpecificUse of emetogenic regimens such as:AC (anthracycline + cyclophosphamide)Carboplatin-based regimensCisplatin-based regimensCyclophosphamide-based regimensFOLFOX/FOLFIRI (oxaliplatin + leucovorin + 5-fluorouracil/irinotecan + leucovorin + 5-fluorouracil)ABVD (doxorubicin + bleomycin + vinblastine + dacarbazine)Short IV infusion timeRepeated cycles of chemotherapy

NCCN, 2014a; Basch et al, 2011.Slide20

Cisplatin: Prototypical Highly Emetogenic ChemotherapyCisplatin is the cornerstone of therapy for many cancersRisk of emesis is universalAgent causes emesis in all patients (there is >99% risk without antiemetics)Well-characterized emetogenic profile serves as a model for antiemetic testingEfficacy shown with cisplatin is predictive of antiemetic efficacy with other chemotherapy drugs

Basch et al, 2011.Slide21

Maximal emetic intensity seen within 24 hours post doseDistinct second phase occurs during Days 2–5 post chemotherapy

Cisplatin: Biphasic Pattern of CINV

Tavorath & Hesketh, 1996; Wilder-Smith et al, 1993.Slide22

Comparison of Biphasic and Monophasic Patterns of Emesis

Martin, 1996.Slide23

Considerations While Selecting the Right Initial AntiemeticEmetogenicity of chemotherapeutic regimen Side-effect profile of antiemetic(s)Other symptomsCostEase of administrationSlide24

High Emetogenic Potential of Selected Antineoplastic AgentsDrugs with >90% emetic risk:CisplatinDacarbazineStreptozocinCyclophosphamide ≥1,500 mg/m2Ifosfamide ≥2 g/m2 per doseDoxorubicin ≥60 mg/m2Adriamycin cyclophosphamide (AC) combination defined as either doxorubicin or epirubicin with cyclophosphamide

NCCN, 2014; Basch et al, 2011; Roila et al, 2010.Slide25

Moderate Emetogenic Potential of Selected Antineoplastic AgentsDrugs with 30–90% emetic risk:OxaliplatinCyclophosphamide ≤1500 mg/m2CarboplatinIfosfamide <2 g/m2 per doseIrinotecanCytarabine >200 mg/m2Anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin)Methotrexate ≥250 mg/m2

NCCN, 2014; Basch et al, 2011; Roila et al, 2010.Slide26

Low Emetogenic Potential of Selected Antineoplastic AgentsDrugs with 10–30% emetic risk:Cytarabine (low dose)GemcitabineTopotecanPaclitaxelDocetaxelPemetrexed

NCCN, 2014; Basch et al, 2011; Roila et al, 2010.Slide27

Minimal Emetogenic Potential of Selected Antineoplastic AgentsDrugs with <10% emetic risk:VincristineVinblastineVinorelbineFludarabineBleomycinRituximabBevacizumabTrastuzumabCetuximab

NCCN, 2014; Basch et al, 2011; Roila et al, 2010.Slide28

Anticholinergics: scopolamine transdermal patchAntihistamines: diphenhydramineBarbiturates: pentobarbital, secobarbitalBenzodiazepines: lorazepamButyrophenones: droperidol, haloperidolCannabinoids: dronabinol, nabilonePhenothiazines: prochlorperazine, chlorpromazine, promethazineAtypical antipsychotics: olanzapineAntiemetics Used in CINV Management

NCCN, 2014; Basch et al, 2011; Roila et al, 2010.Slide29

Antiemetics Used in CINV Management (cont.)NK1 inhibitors: aprepitant, fosaprepitantSerotonin antagonists: ondansetron, granisetron, dolasetron mesylate, palonosetronSteroids: dexamethasone, methylprednisoloneSubstituted benzamines: metoclopramide

NCCN, 2014; Basch et al, 2011; Roila et al, 2010.Slide30

Potential Side Effects of AntiemeticsAnticholinergics: dry mouth, drowsiness, blurred vision, disorientation, restlessness, confusionAntihistamines: drowsiness, restlessness (eg, restless legs), confusion, dizziness, blurred vision/diplopia, tinnitus, dry mouth/nose/throat, urinary retention, frequency, rash, hypotension, palpitationsWickham, 2012.Slide31

Potential Side Effects of Antiemetics (cont.)Barbiturates: drowsiness, lethargy, hangover, respiratory depression, Stevens-Johnson syndrome, angioedemaBenzodiazepines: drowsiness, sedation, disorientationButyrophenones: restlessness, sedation, extrapyramidal reactions, respiratory depression, tachycardia, hypotension, prolonged QT interval (time between Q wave and T wave, inversely proportional to heart rate)Wickham, 2012.Slide32

Potential Side Effects of Antiemetics (cont.)Cannabinoids: mood changes; disorientation; dizziness; brief impairment of perception, coordination, and sensory functions; tachycardia; hypotensionNK1 inhibitors: weakness, dizziness, diarrhea, constipation, flatus, abdominal discomfort, reflux symptoms, hiccups, headacheSerotonin antagonists: diarrhea, constipation, headache, increased liver function testsWickham, 2012.Slide33

NCCN5-HT3 (Day 1)+dexamethasone PO or IV (Day 1) and PO (Days 2–4)+aprepitant PO (125 mg Day 1, 80 mg Days 2–3

)

o

r

f

osaprepitant IV (150 mg Day 1 only)

±

lorazepam

PO or IV

o

r

o

lanzapine PO (10 mg Days 1–4)

palonesetron IV (0.25 mg Day 1)

d

examethazone IV (20 mg Day 1)

± lorazepam

Guidelines for CINV Prevention:

Highly Emetogenic Chemotherapy

NCCN, 2014.Slide34

Basch et al, 2011; Roila et al, 2010.

ASCO (American Society of Clinical Oncology)

5-HT

3

(Day 1)

+

d

examethasone

(Days 1–3 or 1–4)

+

a

prepitant PO

(125 mg Day 1, 80 mg Days 2–3)

o

r

f

osaprepitant IV

(150 mg Day 1 only)

MASCC (Multinational Association of Supportive Care in Cancer/ESMO (European Society for Medical Oncology)

5-HT3 (Day 1)+dexamethasone (Days 1–4)+aprepitant PO (125 mg Day 1, 80 mg Days 2–3)orfosaprepitant IV (150 mg Day 1 only)

Guidelines for CINV Prevention: Highly Emetogenic Chemotherapy (cont.)Slide35

NCCNa5-HT3 (Day 1–3)+dexamethasone PO or IV (Days 1–3)+fosaprepitant IV (150 mg Day 1 only)

o

r

o

lanzapine-containing regimen

Guidelines for CINV Prevention:

Moderately Emetogenic Chemotherapy

a

NCCN guidelines classify an antiemetic regimen including aprepitant as Category 2A of evidence (based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate).

NCCN, 2014.Slide36

ASCO5-HT3 (Day 1, palonosetron preferred PO or IV)+dexamethasone PO or IV

(Days 1–3)

b

MASCC/ESMO

a

5-HT

3

(Day 1)

+

d

examethasone PO or IV (Day 1)

+

a

prepitant PO (125 mg Day 1)

+

a

prepitant PO (80

mg

Days 2–3)

cGuidelines for CINV Prevention: Moderately Emetogenic Chemotherapy (cont.)aAnthracycline + cyclophosphamide-based moderately emetogenic chemotherapy.bASCO states that limited evidence supports adding aprepitant to this combination; there was no data on fosaprepitant in moderate-risk settings. If used, aprepitant is dosed at 125 mg on Day 1, 80 mg on Days 2-3. cMASCC level of scientific confidence/consensus = moderate/moderate. ESMO level of evidence/grade of recommendation = II/B.Basch et al, 2011; Roila et al, 2010.Slide37

CINV Prevalent With Some Common HEC Regimens Despite 5-HT

3

Use

a

Reported as CINV.

TAC =

docetaxel

+ doxorubicin + cyclophosphamide; NSCLC = non-small cell lung cancer;

IP = intraperitoneal.

Martin et al, 2005; Manegold et al, 2000; Piccart et al, 2003.Slide38

CINV Prevalent With Some Common MEC Regimens Despite 5-HT

3

Use (cont.)

MEC = moderately emetogenic chemotherapy; TC =

docetaxel

+ cyclophosphamide.

Jones et al, 2006; Mok et al, 2009; Tournigand et al, 2004; Vasey et al, 2004.Slide39

Around-the-clock (ATC) a better option than as needed (prn)Use drug(s) from different class than previously usedNCCN guidelines list specific choices from multiple classes of agentsManagement of Breakthrough of Nausea and Vomiting

NCCN, 2014.Slide40

Atypical antipsychoticOlanzapineBenzodiazepineLorazepamCannabinoidDronabinolNabiloneOtherHaloperidolMetoclopramideScopolamine

NCCN, 2014.

Treatment for Breakthrough Nausea and VomitingSlide41

Treatment for Breakthrough Nausea and Vomiting (cont.)PhenothiazineProchlorperazinePromethazineSerotonin 5-HT3 antagonistsDolasetronGranisetronOndansetronSteroidDexamethasone

NCCN, 2014.Slide42

Prevention and Treatment of Anticipatory EmesisPrevention is keyUse optimal antiemetic therapyBehavioral therapyRelaxation/systemic desensitizationHypnosis/guided imageryMusic therapyAcupuncture/acupressureAlprazolam or lorazepam

NCCN, 2014.Slide43

Physician andNurse Estimates

N = 24

Actual Patient

Results

N = 298

a

Acute emesis incidence (%)

HEC

MEC

17

13

12

13

Delayed emesis incidence (%)

HEC

MEC

22

15

50

28

Perception and Reality:

Control of Emesis

a

67 received HEC, 231 received MEC.

Grunberg et al, 2004.Slide44

MP = metoclopramide.Roila et al, 2000. Acute

g

uidelines: 5-HT

3

+ steroid

Delayed guidelines: Steroid + MCP or 5-HT

3

Are Antiemetic Guidelines Followed?

High risk: cisplatin (N = 206)

Acute

Delayed

Followed

guidelines (%)

77

20

5-HT

3

alone (%)

2229No antiemetic (%)41Slide45

Acute guidelines: 5-HT3 + steroidDelayed guidelines: Steroid + MCP or 5-HT3

Are Antiemetic Guidelines Followed? (cont.)

High risk: non-

cisplatin

[moderate] (N = 1,061)

Roila et al, 2000.

Acute

Delayed

Followed

guidelines (%)

57

4

5-HT

3

alone (%)

40

57

No antiemetic

(%)35Slide46

Acute guidelines: No preventive antiemeticDelayed guidelines: No preventive antiemetic

Roila et al, 2000.

Are Antiemetic Guidelines Followed? (cont.)

Low risk (N = 225)

Acute

Delayed

Followed

guidelines (%)

5

85

5-HT

3

alone (%)

45

5-HT

3

+ steroid (%)

20

11MCP (%)214Slide47

NCCN Guidelines:Principles of CINV ControlCurrent NCCN guidelines include the following principles: Prevention is the goalRisk of CINV lasts for at least 3 days with HEC and 2 days with MECConsider the toxicity of specific antiemetic(s)Choose antiemetic(s) based on emetogenicity of therapy and patient factorsConsider other potential causes of emesis in cancer patients (eg, bowel obstruction, electrolyte imbalance, brain metastases)

NCCN, 2014.Slide48

Risk of Emesis Increases With Number of Risk Factors Despite 5-HT

3

Antagonist Use

Osoba

, Zee, Pater, et al, 1997.Slide49

CINV: Aim for PreventionPrevention of CINV is the goalPatients need protection for the full period of CINV riskAssess patient and chemotherapy factors related to CINV riskThe choice of antiemetic(s) should be based on emetogenicity of therapy and patient risk factorsProvide patient education and counseling tools for both in-office and take-home useThey should be simple and easy to understandConsider a visual analog scale for nausea and patient diaries for vomitingMASCC Antiemesis Tool is available online at http://www.mascc.org/mat

NCCN, 2014; Basch et al, 2011; Roila et al, 2010; Boogaerts et al, 2000;

Osoba

, Zee, Pater, et al, 1997.Slide50

Case Study 1: Delayed CINVMs. DL is a 49-year-old attorney with node-positive invasive ductal carcinoma of the breast, estrogen and progesterone receptor positive, and human epidermal growth factor receptor 2 (HER2) negative. She undergoes a lumpectomyOncologist recommends adjuvant chemotherapy with four cycles of AC chemotherapy: doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 IV Day 1, every 3 weeksPatient is anxious and concerned about any side effects that might keep her from workingSlide51

Case Study 1 (cont.)Which chemotherapy-induced side effects may be particularly important for this patient?Nausea and vomitingAlopeciaNeutropeniaAll of the aboveSlide52

Case Study 1 (cont.)Which patient characteristic can increase the risk for CINV?Female sexAge <50 yearsAnxietyAll of the aboveSlide53

Case Study 1 (cont.)What other risk factors for CINV might be important in this patient?History of motion sicknessHistory of morning sicknessHistory of low alcohol intake (<1.5 oz/d)Slide54

Case Study 1 (cont.)What steps can be taken to prevent CINV in this patient?Make prevention a goal of treatmentImplement optimal prophylaxis to prevent both acute and delayed CINVStart antiemetic therapy before chemotherapySlide55

Case Study 2: Breakthrough CINVMr. CW is a 72-year-old engineer with stage IIA adenocarcinoma of the lung; status post right-upper lobectomy and mediastinal lymphadenopathyOncologist recommends adjuvant chemotherapy with docetaxel 75 mg/m2 IV and cisplatin 75 mg/m2 IV Day 1, every 3 weeks for four cyclesSlide56

Case Study 2 (cont.)Mr. CW’s regimen is considered highly emetogenic.TrueFalseSlide57

Case Study 2 (cont.)Oncologist reviews side effects associated with chemotherapy regimenTells patient that 75% of patients experience some nausea and vomiting (grades 1 and 2) while approximately 24% experience severe nausea and vomiting (grades 3 and 4)Patient states he is very anxious about occurrence of nausea and vomitingSlide58

Case Study 2 (cont.)Since patient is receiving a regimen considered highly emetogenic, oncologist gives patient the following antiemetic regimen prior to starting chemotherapy:Fosaprepitant 150 mg IV Day 1Palonosetron 0.25 mg IV Day 1Dexamethasone 12 mg IV Day 1 and 8 mg PO Day 2, then 8 mg PO twice daily Days 3–4Patient also given lorazepam 0.5 mg PO every 6 hours Days 1–4Slide59

Case Study 2 (cont.)Mr. CW experiences some nausea without vomiting during first 24 hours after chemotherapyExperiences progressive nausea and vomiting for next 96 hoursForty-eight hours after he received chemotherapy, patient calls oncology nurse, who recommends additional antiemetics for breakthrough nausea and vomitingSlide60

Case Study 2 (cont.)What regimen would you recommend for Mr. CW’s breakthrough nausea and vomiting?Add one agent from a different class to current regimenConsider increasing dose of lorazepamSlide61

Case Study 3: Refractory CINVMs. WB is a 56-year-old woman with stage IV ovarian carcinoma with bulky abdominal metastases as well as liver metastasesECOG (Eastern Cooperative Oncology Group) performance status 2Complains of abdominal pain for which she is receiving narcoticsStarted on paclitaxel 175 mg/m2 IV Day 1 and carboplatin with area under the curve (AUC) 6 IV Day 1 given every 3 weeksSlide62

Case Study 3 (cont.)With the first cycle of chemotherapy, Ms. WB received palonosetron 0.25 mg IV Day 1 and dexamethasone 12 mg IV Day 1Developed nausea and vomiting on the evening of Day 1 extending through Day 2With the second cycle, fosaprepitant 150 mg IV Day 1 was added to the previous antiemetic regimen

D

eveloped

more nausea and vomiting

that continued

for a

weekSlide63

Case Study 3 (cont.)What is the appropriate management of refractory nausea and vomiting?Investigate other causes of nausea and vomiting (eg, liver metastases, bowel obstruction)Increase doses of antiemeticsSwitch antiemeticsa and cSlide64

Antiemetic Treatment: Current Status and Future ConsiderationsMarked advances in antiemetic therapy have occurred over past few decades and recentlyBest antiemetic control occurs when efficacy from clinical trials is emulated in clinical practiceAdvances have had major impact on patient QOL and patterns of treatment (move to ambulatory chemotherapy)Future studies need to concentrate on mechanisms of resistance and identification of patients at riskResearch is needed on understanding and controlling nauseaNew agents are neededSlide65

Aapro MS, Molassiotis A, and Olver I (2005). Anticipatory nausea and vomiting. Support Care Cancer, 13(2):117-121.Andrews PLR, Naylor RJ, and Joss RA (1998). Neuropharmocology of emesis and its relevance to anti-emetic therapy. Consensus and controversies. Support Care Cancer, 6(3):197-203.Basch E, Prestrud AA, Hesketh PJ, et al (2011). Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol, 29(31):4189-4198. DOI:10.1200/JCO.2010.34.4614.Bloechl-Daum B, Deuson RR, Mavros P, et al (2006). Delayed nausea and vomiting continue to reduce patients’ quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. J Clin Oncol, 24(27):4472-4478.

Boogaerts

JG,

Vanacker

, E, Seidel L, et al (2000). Assessment of postoperative nausea using a visual analogue scale.

Acta

Anaesthesiol

Scand

, 44(4)470-474

.

Börjeson

S,

Hursti

TJ,

Tishelman

C, et al (2002). Treatment of nausea and emesis during cancer chemotherapy.

Discrepancies

between antiemetic effect and well-being. J Pain Symptom Manage, 24(3):345-358.de Boer-Dennert M, de Wit R, Schmitz PI, et al (1997). Patient perceptions of the side-effects of chemotherapy: the influence of 5HT3 antagonists. Br J Cancer, 76(8):1057.DeVane CL (2001). Substance P: a new era, a new role. Pharmacotherapy, 21(9):1061-1069. Fernández-Ortega P, Caloto MT, Chirveches E, et al (2012). Chemotherapy-induced nausea and vomiting in clinical practice: impact on patients' quality of life. Support Care Cancer, 20(12):3141-3148. Grunberg SM (2012). Patient-centered management of chemotherapy-induced nausea and vomiting. Cancer Control, 19(suppl):10-15. Grunberg SM, Deuson RR, Mavros P, et al (2004). Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer, 100(10):2261-2268.Hargreaves R (2002). Imaging substance P receptors (NK1) in the living human brain using positron emission tomography. J Clin Psychiatry, 63(suppl 11):18-24.Hesketh PJ (2001). Potential role of the NK1 receptor antagonists in chemotherapy-induced nausea and vomiting. Support Care Cancer, 9(5):350-354.ReferencesSlide66

Hesketh PJ, Van Belle S, Aapro M et al (2003). Differential involvement of neurotransmitters through the time course of cisplatin-induced emesis as revealed by therapy with specific receptor antagonists. Eur J Cancer, 39(8):1074-1080.Jones SE, Savin MA, Holmes FA, et al (2006). Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol, 24(31):5381-5387. Lau PM, Stewart K, and Dooley M (2004). The ten most common adverse drug reactions (ADRs) in oncology patients: do they matter to you? Support Care Cancer, 12(9):626-633. Manegold C, Gatzemeier U, von Pawel J, et al (2000). Front-line treatment of advanced non-small-cell lung cancer with MTA (LY231514, pemetrexed disodium, ALIMTA) and cisplatin: a multicenter phase II trial.

Ann

Oncol

, 11(4):435-440

.

Martin M (1996). The severity and pattern of emesis following cytotoxic agents.

Oncology

, 53(

suppl

1):26-31.

Martin M,

Pienkowski

T, Mackey J, et al (2005). Adjuvant docetaxel for node-positive breast cancer.

N

Engl

J Med

, 352(22):2302-2313.

Miner WD and Sanger GJ (1986).

Inhibition

of cisplatin-induced vomiting by selective 5-hydroxytryptamine M-receptor antagonism. Br J Pharmacol, 88(3):497-499.Mok TS, Wu YL, Thongprasert S, et al (2009). Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med, 361:947-957. DOI:10.1056/NEJMoa0810699National Comprehensive Cancer Network (2014). NCCN Clinical Practice Guidelines in Oncology: Antiemesis. Accessed on: March 21, 2014. Available at: http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdfNeijt JP, Engelholm SA, Tuxen MK, et al (2000). Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol, 18(17):3084-3092.Osoba D, Zee B, Pater J, et al (1997). Determinants of postchemotherapy nausea and vomiting in patients with cancer. J Clin Oncol, 15(1):116-123.ReferencesSlide67

Osoba D, Zee B, Warr D, et al (1997). Effect of postchemotherapy nausea and vomiting on health-related quality of life. Support Care Cancer, 5(4):307-313. Piccart MJ, Floquet A, Scarfone G, et al (2003). Intraperitoneal cisplatin versus no further treatment: 8-year results of EORTC 55875, a randomized phase III study in ovarian cancer patients with a pathologically complete remission after platinum-based intravenous chemotherapy. Int J Gynecol Cancer, 13(suppl 2):196-203.Roila F, De Angelis V, Patola L, et al (2000). Antiemetic prescriptions in 77 Italian oncological centers after the MASCC Consensus Conference. Support Care Cancer, 8:241.Roila

F,

Herrstedt

J, Aapro M, et al (2010). Guideline update

for

MASCC

and

ESMO

in the prevention of chemotherapy and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference.

Ann

Oncol

, 21(

suppl

5):v232-v243

.

Sun CC,

Bodurka

DC, Weaver CB, et al (2005). Rankings and symptom assessments of side effects from chemotherapy: insights from experienced patients with ovarian cancer.

Support Care Cancer, 13(4):219-227.Tattersall FD, Rycroft W, Francis B, et al (1996). Tachykinin NK1 receptor antagonists act centrally to inhibit emesis induced by the chemotherapeutic agent cisplatin in ferrets. Neuropharmacology, 35(8):1121-1129.Tavorath R and Hesketh PJ (1996). Drug treatment of chemotherapy-induced delayed emesis. Drugs, 52(5):639-648.Tournigand C, André T, Achille E, et al (2004). FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol, 22(2):229-237Vasey PA, Jayson GC, Gordon A, et al (2004). Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst, 96(22):1682-1691.Wickham R (2012). Evolving treatment paradigms for chemotherapy-induced nausea and vomiting. Cancer Control, 19(2 suppl):3-9.Wilder-Smith OH, Borgeat A, Chappuis P, et al (1993). Urinary serotonin metabolite excretion during cisplatin chemotherapy. Cancer, 72(7):2239-2241.References