Evidence Table 5

Chemotherapy active-control trials

Author
Year
Setting
Chemo Level
Type of Test
DesignSubpopulationExclusion criteriaInterventionAllowed other medicationRun-in/Wash outAge Gender EthnicityScreened/Eligible/EnrolledWithdrawn/Lost to fu/AnalyzedOther population characteristicsResultsAdverse eventsComments
Bhatia
2004
Single Center
5
Rotterdam
RCT
Observer blind
Parallel
NRPts excluded if any applied: severe concurrent illness, vomiting due to some other cause, antiemetic therapy administered concurrently or in the 24 preceding chemo, administration of benzodiazepines except when given for night sedation, vomiting in 24h before chemo, pregnant or lactating women, concurrent radiation therapy, impaired renal function (serum creatinine >2.0 mg/dL) jaundice (serum bilirubin >2.0 mg/dL) or an elevated aminotranserase level (SGOT/SGPT> 2X ULN).There were 6 groups: I, II, IIIa, IIIb IVa, IVb

Ond: 8 mg iv (30 min prior to each cisplatin administration); 8 mg ond po tid for 5 days
this Ond regimen given to II, IVa, IVb

Meto: 20 mg iv (30 min prior to cisplatin); 20 mg po tid for 5 days
this meto regiment given to I, IIIa, IIIb
Dex 8 mg iv given to groups IIIb and IVb along with study medsNo run-in; washout-no antiemetics within 24h of study entryMean Age: 45.7y

0% male
NR/NR/80NR/NR/80Malignancy: Head and Neck 54%
Cervix 41%
Others 5%
Tumour surgery: Yes: 14% vs No: 86%
Alcohol intake: none 80%
<7 units/wk 14%
>7 units/wk 6%
% smokers: 49%
Karnofsky Performance mean score: 96.9 (+/−4.7)
% with history of motion sickness: 0%
Comparisons are for I (M+C-20) vs II (O+C-20) vs IIIa (M+C-60) vs IVa ( O+C-60) vs IIIb (M+D+C-60)
Quality of Life scores
Psychological subscale (QoL): (0= “not at all”, 1= “a little”, 2= “somewhat”, 3= “very much”)
Day 0 score(Day 5 score): 1.1(1.0) vs 2.1(1.8) vs 2.3(1.6) vs 2.9(2.9) vs 2.7(1.8), NS
Physical subscale (QoL): (0= “not at all”, 1= “a little”, 2= “somewhat”, 3= “very much”)
Day 0 score(Day 5 score): 1.2(1.0) vs 1.2(1.2) vs 1.7(2.2) vs 1.9(2.2) vs 1.9(1.5), NS
Functional subscale (QoL): (0= “without help”, 1= “w/o help with difficulty”, 2= “only with help”, 3= “unable”)
Day 0 score(Day 5 score): 1.5(1.5) vs 2.4(2.4) vs 1.9(1.9) vs 1.0(1.0) vs 2.8(2.8), NS
Patient satisfaction mean scores: (0= “not at all satisfied” to 100= “totally satisfied”)
75.7 vs 86 vs 45 vs 65 vs 68; IIIb vs IVb, p<0.02
AEs reported (a total of 39 AEs were reported by 20 pts; incidence =25%)
Results given as all Ond groups (n=40) vs all Met groups (n=40), p = NR
Dystonia/akathisia: 0% vs 0%
Constipation: 17.5% vs 2.5%
Headache: 15% vs 12.5%
Heartburn: 10% vs 5%
Weakness: 5% vs 12.5%
Epigastric pain: 5% vs 7.5%
Nervousness: 2.5% vs 2.5%
Chemo: All pts received a regimen consisting of cisplatin, bleomycin and 5- flurouracil, making the chemo uniform in all the patients. Pts were randomized according to a table of random numbers to receive either low dose cisplatin regimen (I and II) or high dose cisplatin (III and IV). In high dose cisplatin, pts given 60 mg/m2 cisplatin iv as a single dose on 1st day; in low dose cisplatin, cisplatin was split into 3 iv doses of 20 mg/m2 each on 3 consecutive days. Cisplatin was administered as continuous iv infusion over 1h. All pts also received bleomycin 15 mg iv on 1st and 5th day, and 5-fluorouracil 500 mg iv for 5 days.
Lachaine
1999
Single Center
4
EORTC, QLC-3
Not
Randomized
Not blinded
Parallel
women, breast
cancer
NRA: Ond 21mg (avg dose for Day 1)

B: Metoclopramide 306mg
A: for 91% of these pts, Dex ~19 mg on day 1 and 53% received 1 mg lorazepam;Mean age: 55.4y

0% male

Ethnicity: NR
NR/NR/585/NR/52Average Body Surface: 1.68 m2 (+/− 8.5 m2)
Average dose cyclophosphamide: 990 mg (+/− 157mg)
Language: French Speaking: 41%; English Speaking: 50%
Chemo types:
Cyclo + dox: 57%; CMF: 24%; FAC: 3%;
Cyclo + carboplatin: 3%; Cyclo + epir 2%
Mean change in ETORCG scores between baseline and Day 3
Physical: −19 vs. −35, p=NS
Role Functioning: −2 vs. −13, p=0.002
Emotional: +8 vs. +5, p=NS
Cognitive: −5 vs. −13, p=NS
Social: −9 vs. −2, p=NS
Global health/QoL: −21 vs. −22, p=0.28
Nausea/vomiting: 13 vs. 11, p=NS
In meto group, 4 pts had serious AEs which caused them to stop the antiemetic
(no other data on these AEs given)

0 pts had serious AEs requiring treatment cessation in Ond group
The most frequent chemotherapies were the combination of cyclophosphamide and doxorubicin (64%), and the combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) (27%). Two patients received cyclophosphamide. Doxorubicin and 5-fluorouracil (FAC).; two received cyclophosphamide and carboplatin; and one received cyclophosphamide and epirubicin. The type of chemotherapy was not significantly different between the two groups.
Clavel
1995
Multicenter
4
FLIE; FLIC
DB RCT
Parallel
women, breast
cancer
Pts not eligible if any of the following applied: serious disease other than the cancer being treated, another cause of nausea or vomiting other than the chemo, a clinical hepatic disorder, a persistent chronic alcoholism, emesis or anti-emetic treatment during 24h preceding study entry.A: Ond po (tablet) 16mg (8 mg bid)
B: Alizapride iv 150mg
NoNo run-in; washout-no antiemetics within 24h of study entryMean Age: 51.5y

0%male

NR
NR/259/2595/NR/254Mean body surface area: 1.66 (+/− 0.01) m2
Alcohol consumption >4 units/day: 0%
Histological type: Ductal: 87%
Lobular: 7%
Colloid: 0%
Other: 4%
Chemotherapy regimens: FEC: 79%, FAC: 20%
all data given as Ond vs Aliz
Pt nausea grade (0= none, 100= nausea as bad as it could be): 25.8 vs 44.5 (p<0.0001)
Pt satisfaction: pts wished to receive same treatment during next chemo regimen: 83% vs 54%, p<0.001
For FLIC and FLIE, a lower score means a better QoL for the pt
Mean differences in FLIC scores (change from baseline to post-chemo):
−0.55 vs 0–.73, p=NS
Mean differences in FLIE scores (change from baseline to post-chemo):
−1.45 vs −1.93, p=0.04
AEs were minor in both groups, data only given for headache
Headache: ond − 1.6% vs aliz − 2.3%, p = NR
Soukop
1992
Multicenter
4
Rotterdam
DB RCT
Parallel
women, breast cancerPts excluded if any of the following applied: severe concurrent illness, gastrintestinal obstruction, central nervous system metastases, anti- emetic therapy administered concurrently or in 24 h before chemo, administration of benzodiazepines except when given for night sedation, vomiting in th 24h before chemo, cisplatin-containing regimens, and pregnancy.O: Ond 8mg
M: metoclopramide 60mg
Dex 16 mg iv one time onlyNo run-in; washout-no antiemetics within 24h of study entryMean Age: 48.58y

0% male
NR/187/1874/NR/183Height mean: 161.0 (+/− 6.71) cm
range: 140–181 cm
Mean weight: 65.14 (+/− 12.85) kg
range: 40.5–135.0 kg
Surface area (SA) mean: 1.66(+/− 0.17) m2
SA range: 1.2 – 2.4 m2
Quality of Life: Rotterdam subscales
Differences in scores between baseline and Day 5, O vs M
Psychological: +25% vs +12%, p=0.002
Physical: −24% vs −24%, p=NS
Change in functional activity: 0 vs 0
Met: 15% withdrawn due to extrapyramidal symptoms (EPS).
4% reported EPS (restlessness, agitation) of a less severe nature that did not lead to withdrawal
Ond: 0% reported EPS

Skin rashes: Ond - 4% vs Met - 0%
Allergy: Ond - 1% vs Met - 0% (likely caused by methotrexate, not Ond)

1 pts showed elevated liver enzymes in 2nd course but no further abnormalities in courses 3–6

Most common AEs, O vs M
EPS: 0% vs 19%
Diarrhea: 0% vs 14%
Constipation: 19% vs 5%
Headache: 13% vs 9%
Crucitt
1996
Multicenter
4
FLIE
DB RCT
Parallel
women, breast cancerPts who had received chemo or ond at any time during the past as well as pts who had received any medication with potential antiemetic activity (phenothiazines, butyrophenones, hydroxyzine, lorazepam, cannabinoids, metoclopramide, corticosteroids, or trimethobenzamide) within 24h before the first dose of the study drug or during 3 days after initiation of chemo were excluded.O: Ond po 16mg (8 mg bid) for up to 3 days
P: Prochlorperazine po 20mg (10 mg bid ) for up to 3 days
NoNo run-in; washout-no drugs with antiemetic activity within 24h of study entryMean Age: 57.8y

10% male

White: 87%
Black: 9%
Other: 4%
NR/NR/13320/NR/113 (133 for safety)Mean body weight = 72 kg (range: 43–149 kg)
Chemotherapy regimen: CYC/DOX:10%
CYC/DOX/FU 24:18%
CYC/DOX/FU/VCR: 1%; CYC/DOX/VCR: 4%
CYC/DOX/VCR/prednisone: 8%
CYC/DOX/VP16: 1%; DOX/FU:1%
CYC/methotrexate/FU: 58%; Data Not Available:1%
Alcohol consumption:
< 5 drinks/y 66%; < 7 drinks/wk 30%
1–4 drinks/d 3%; > 5 drinks/d 0%
Prior heavy use: > 5 drinks/d: 1%
Ondansetron vs Prochlorperazine
FLIE scores (100 is highest possible score)
decrease in nausea subscore, baseline to final score:
−25.3 vs −33.5, p=NS
decrease in vomiting subscore, baseline to final score:
−7.9 vs −26.3, p=0.01 for O vs P
Data given as O vs P
Headache: 16% vs 3%, p<0.05
No other AE occurred in ≥ 3% in either group

3 pts were withdrawn from study due to AEs: 2 pts (1 in O and 1 in P) were withdrawn due to injection site reaction (iv infiltration due to chemo; considered not to be related to administration of study drug); 1 P pt had persistent vomiting that required hospitalization (considered unlikely to be related to the study drug)
Luisi 2006Pts excluded if had renal or hepatic abnormalities, or chronic vomiting, or were given oral antiemetics on the day chemotherapy was administered.G: Granisetron: 50μg/kg in a single dose over 5 minute period

M: 2 mg/kg metoclopramide plus an 8-hour infusion of 5 mg/kg dimenhydrinate
Mean age: 14 yrs
Range: 7–19 yrs

% male: NR

From: Evidence Tables

Cover of Drug Class Review: Newer Antiemetics
Drug Class Review: Newer Antiemetics: Final Report Update 1 [Internet].
Peterson K, McDonagh M, Carson S, et al.
Portland (OR): Oregon Health & Science University; 2009 Jan.
Copyright © 2008, Oregon Health & Science University, Portland, Oregon.

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