Chemotherapy-induced neurotoxicity in the treatment of gynecological cancers: State of art and an innovative approach for prevention

Table 1 Incidence of chemotherapy-induced peripheral neuropathy

Trail	Indication	No. of patients	Treatment	Grade 1 (%)	Grade 2 (%)	Grade 3 (%)
AGO OVAR 3[35]	FIGO IIB-IV fist line	388	CP	39	28	6.7
		384	PP	33	36	12.5
JGOG[29]	FIGO II-IV fist line	319	CP			20 (6)
		312	C-P			21 (7)
MITO 4[27]	FIGO IC-IV fist line	120	CP	51 (42)	13 (11)	1 (1)
MITO 2[26]	FIGO IC-IV fist line	407	CP	115 (28)	64 (16)	12 (3)
		396	C-PLD	47 (12)	11 (3)	1 (< 1)
MITO 7[28]	FIGO IC-IV fist line	404	CP	95 (24)	58 (15)	8 (2)
		406	CP weekly	98 (25)	24 (6)	0
ICON 4[2]	Platinum-sensitive relapse > 6 mo	410	P-based		4 (1)
		392	CP/PP		76 (20)

CP: Carboplatin area under the curve (AUC) 5/6 mg/mL per min plus paclitaxel 175-185 mg/mq every 3 wk; CP weekly: Carboplatin AUC 2 mg/mL per min plus paclitaxel 60 mg/mq every week; C-P: Carboplatin AUC 6 mg/mL per min every 3 wk plus paclitaxel 80 mg/mq on days 1, 8, 15, and every 21 d; C-PLD: Carboplatin AUC 5 mg/mL per minute plus pegylated liposomial doxorubicin 30 mg/mq every 3 wk; P-based: Cisplatin (50 mg/mq in combination with other drugs or 75 mg/mq as a single agent)/carboplatin AUC 5/6 mg/mL every 3 wk; PP: Cisplatin 75 mg/mq plus paclitaxel 175 mg/mq every 3 wk.

Table 2 Patient characteristics

Characteristics	n (%)
Age, mean (range)	61 (35-74)
Gyneacologic cancer	44
Risk factors
None	38 (86.3)
Diabetes	3 (6.8)
Arthrosis and diabetes	1 (2.3)
Hyphotyroidsm	2 (4.6)

Table 3 Chemotherapy-induced peripheral neuropathy per cycle, according to Common Terminology Criteria for Adverse Events (version 4.0)

Chemotherapy	Number of patients	Reported CIPN, n (%)
		Grade 0	Grade 1	Grade ≥ 2
Cycle 1	44	44 (100)	0 (0)	0 (0)
Cycle 2	44	43 (97.7)	0 (0)	0 (0)
Cycle 3	43	40 (93.0)	1 (2.3)	0 (0)
Cycle 4	41	33 (80.5)	1 (2.4)	0 (0)
Cycle 5	34	22 (64.7)	1 (2.9)	1 (2.9)
Cycle 6	24	20 (83.3)	2 (8.3)	1 (4.2)

CIPN: Chemotherapy-induced peripheral neuropathy.

Table 4 Chemotherapy (paclitaxel) dose changes during hilotherapy treatment

	Patients, n (%)
Completed scheduled CP cycle1	37 (84.1)
Paclitaxel dose reduction/discontinuation	9 (20)
Reason for Paclitaxel reduction/discontinuation	3 (6.8) hematological toxicity; 3 (6.8) disease progression; 2 (4.5) paclitaxel allergic reaction; 1 (2.2) CIPN ≥ 2

¹Carboplatin area under the curve 5 mg/mL per min plus paclitaxel at 175 mg/mq every 3 wk.

CP: Carboplatin/paclitaxel; CIPN: Chemotherapy-induced peripheral neuropathy.