A Phase II single-arm trial of palonosetron for the prevention of acute and delayed chemotherapy-induced nausea and vomiting in malignant glioma patients receiving multidose irinotecan in combination with bevacizumab

Figures & data

Table 1 Study schema for biweekly (every 2 weeks) administration of chemotherapy over a 6-week cycle

Day	−14 to 1	1	2	3	4	5	15
Screening*	X
NCI toxicity	X	X	X	X	X	X
NCI toxicity telephone assessment							X
Osoba NV-5 modules	X	X	X	X	X	X
M-FLIE	X	X	X	X	X	X
FACIT-F	X	X	X	X	X	X
PAL 0.25 mg IV		X
DEX 10 mg IV		X
Irinotecan		X
Bevacizumab		X

Note:

* Screening (baseline) criteria only completed once at the beginning of the 6-week cycle.

Abbreviations: NCI, National Cancer Institute; M-FLIE, Modified Functional Living Index—emesis; FACIT-F, Functional Assessment of Chronic Illness Therapy-fatigue; PAL, palonosetron; DEX, dexamethasone.

Table 2 Characteristics of patients in the study (n=63)

Patient characteristics (continuous variables)	Mean (SD)	Range (min–max)
Age (years)	53.2 (13.1)	28–75
Steroid dose at baseline (mg)	5.3 (4.4)	0.9–16
Patient characteristics (categorical variables)	n	%
Sex
Female	21	33.3
Male	42	66.7
Race/ethnicity
White	58	92.1
Black/African-American	3	4.8
Asian	1	1.6
White, Hispanic	1	1.6
Initial diagnosis
GBM	44	69.9
AA	9	14.7
AO	6	9.5
Mixed glioma	2	3.2
Well-differentiated infiltrated glioma	2	3.2
Pleomorphic xanthoastrocytoma with anaplastic features	1	1.6
KPS score
≥90%	33	52.3
<90%	30	47.7
AED status
EIAED taken	17	27.0
Non-EIAED taken	26	41.3
No AED taken	20	31.7
Steroid use at baseline
Yes	23	36.5
No	40	63.5

Abbreviations: SD, standard deviation; GBM, glioblastoma multiforme; AA, anaplastic astrocytoma; AO, anaplastic oligodendroglioma; KPS, Karnofsky Performance Scale; AED, antiepileptic drug; EIAED, enzyme-inducing AED.

Table 3 CINV complete response rates (acute, delayed, and overall), by dose

Time point	Dose 1 (week 1; n=53)		Dose 2 (week 3; n=44)		Dose 3 (week 5; n=37)
	n	Percentage (95% CI)	n	Percentage (95% CI)	n	Percentage (95% CI)
Complete response rate (CINV): percentage of patients with no vomiting and no antiemetic rescue by dose
Acute (day 1)	32a	62 (47, 75)	30	68 (52, 81)	26	70 (53, 84)
Delayed (days 2–5)	33	62 (48, 75)	29	66 (50, 80)	26	70 (53, 84)
Overall (days 1–5)	25	47 (33, 61)	25	57 (41, 72)	23	62 (45, 78)
Vomiting response rate (CIV): percentage of patients with no vomiting event by dose
Acute (day 1)	46a	89 (77, 96)	40	91 (78, 97)	33	89 (75, 97)
Delayed (days 2–5)	46a	89 (77, 96)	38a	88 (75, 96)	31	84 (68, 94)
Overall (days 1–5)	42	79 (66, 89)	36a	84 (69, 93)	28	76 (59, 88)
Nausea response rate (CIN): percentage of patients with no nausea reported by dose
Acute (day 1)	31a	60 (45, 73)	29	66 (50, 80)	22	59 (42, 75)
Delayed (days 2–5)	29	55 (40, 68)	26	59 (43, 74)	21	57 (39, 73)
Overall (days 1–5)	28	53 (39, 67)	25	57 (41, 72)	19	51 (34, 68)

Note:

a One patient missing a response, so denominator one less than reported in the total for the week.

Abbreviations: CINV, chemotherapy-induced nausea and vomiting; CI, confidence interval; CIV, chemotherapy-induced vomiting; CIN, chemotherapy-induced nausea.

Table 4 Overall CINV CR rates (across all doses over 6 weeks)a

Overall (across all 3 doses over 6 weeks)
Time point	Total	CR (n)	CR (%)	95% CI
Acute response (day 1)	37	22	59	42, 75
Delayed response (days 2–5)	37	19	51	34, 68
Overall response (days 1–5)	37	14	38	22, 55

Note:

a Includes only patients with no missing CINV data for all doses over 3 weeks.

Abbreviations: CINV, chemotherapy-induced nausea and vomiting; CR, complete response; CI, confidence interval.

Table 5 M-FLIE: mean change in total score from baseline after dose 1

Time point	n	Total M-FLIE score		Change from baseline (day X – baseline)
		Mean	95% CI	Mean	95% CI
Baseline	52	123	119, 126	–	–
Day 1	49	112	105, 120	−11.0	−17, −3.9
Day 2	51	114	106, 121	−10.0	−17, −3.5
Day 3	51	119	115, 123	−4.8	−8.9, −0.8
Day 4	51	121	116, 125	−3.6	−7.9, 0.8
Day 5	51	122	119, 125	−2.0	−5.6, 1.7
Baseline	52	123	119, 126	–	–
Acute (day 1)	49	112	105, 120	−11.0	−17, −3.9
Delayed (days 2–5)	51	119	115, 123	−5.2	−9.1, −1.4
Overall (days 1–5)	52	117	112, 121	−6.1	−10, −2.0

Note: Higher scores indicate better quality of life.

Abbreviations: M-FLIE, Modified Functional Living Index–emesis; CI, confidence interval.

Table 6 FACIT-F: Mean change in total score from baseline after dose 1

Time point	n	Total FACIT score		Change from baseline (day X – baseline)
		Mean	95% CI	Mean	95% CI
Baseline	48	37.0	34.2, 39.9	–	–
Day 1	46	31.3	27.6, 34.9	−5.6	−8.8, −2.4
Day 2	45	32.8	28.8, 34.9	−4.2	−7.3, −1.1
Day 3	47	34.5	31.0, 38.0	−2.7	−5.6, 0.1
Day 4	47	34.8	31.4, 38.1	−2.5	−5.4, 0.4
Day 5	47	35.1	31.6, 38.6	−2.2	−5.1, 0.8
Baseline	48	37.0	34.2, 39.9	–	–
Acute (day 1)	46	31.3	27.6, 34.9	−5.6	−8.8, −2.4
Delayed (days 2–5)	47	34.4	31.0, 37.7	−2.9	−5.5, 0.2
Overall (days 1–5)	48	33.5	30.3, 36.8	−3.5	−6.1, −0.9

Note: Higher scores indicate better quality of life.

Abbreviations: FACIT-F, Functional Assessment of Chronic Illness Therapy-fatigue; CI, confidence interval.

Table 7 Impact of CINV on HR-QoL in malignant glioma patients, based on standardized scores from the NV-5 nausea and vomiting/retching modules

Dose	Acute impact of CINV (day 1): patients with a maximum standardized score of zeroa	Delayed impact of CINV (days 2–5): patients with a maximum standardized score of zeroa for the entire period
	n (%)	n (%)
NV-5 nausea module
Dose 1 (n=52)	33 (63)	32 (62)
Dose 2 (n=44)	31 (70)	25 (57)
Dose 3 (n=37)	22 (59)	22 (59)
NV-5 vomiting/retching module
Dose 1 (n=52)	46 (88)	45 (87)
Dose 2 (n=44)	40 (91)	37 (84)
Dose 3 (n=37)	31 (84)	31 (84)

Notes:

a In each NV-5 module, patients with a maximum standardized score of 0 were those who reported no impact of a chemotherapy-induced symptom (either nausea or vomiting/retching) on QoL during the acute (day 1) or delayed (days 2–5) phase. All other patients reported that the symptom had a negative impact on their QoL during the same phase.

Abbreviations: CINV, chemotherapy-induced nausea and vomiting; HR-QoL, health-related quality of life.