Chiu et al.‎ [107]

Mesenchymal stem cells (MSC)

Mice intra-peritoneally treated with cisplatin, followed by intra-nasal administration of MSC

- Cisplatin treatment caused deteriorations in executive function, spatial memory and working memory, as measured via the puzzle box test (pBT), the NPORT and the Y-maze test, respectively (p < 0.05).

- Intra-nasal administration of MSC normalized performance levels in the above-described cognitive tests.

Pharmacologic Interventions, Clinical Studies


Study Design

Intervention Investigated

Study Population


Lawrence et al.‎‎ [111]

Randomized, placebo-controlled pilot study


BC patients (n = 47) 1 - 5 years following receipt of adjuvant chemotherapy (>4 cycles)

- Patients receiving daily donepezil (5 mg PO for 6 weeks, followed by 10mg PO for an additional 18 weeks) performed significantly better than placebo in two memory parameters of the Hopkins Verbal Learning Test Revised: Total Recall (p = 0.033) and Discrimination (p = 0.036).

Kohli et al.‎‎ [112]

Open-label followed by placebo-controlled randomization


BC patients (n = 68) who had previously received chemotherapy and/or radiotherapy and have reported symptoms of Chemotherapy-Related Fatigue (CRF)

- Phase 1 (open-label): patients who have received modafinil 200 mg PO once daily for 4 weeks in an open-label fashion demonstrated significant improvements in speed of memory (p = 0.0073) and episodic memory (p < 0.0001) compared to baseline. No effect was observed in the domains of attention (p = 0.0568) and working memory (p = 0.2475).

- Phase 2 (randomized): patients randomized to modafinil showed greater improvements in speed of memory (p = 0.029), episodic memory (p = 0.0151) and continuity of attention (p = 0.0101) compared to placebo.

Lundorff et al.‎‎ [113]

Double-blind, randomized, cross-over trial


Patients with various advanced solid malignancies (n = 36), and a tiredness score of >50 mm on the Edmonton Symptoms Assessment System (ESAS).*

- Modafinil elicited significantly superior results compared with placebo in two cognitive tests: Finger Tapping Test (FTT) for evaluation of psychomotor speed (p = 0.006) and the Trail Making Test (TST) of visual attention and task switching (p = 0.042)

Blackhall et al.‎‎ [114]

Open-label pilot study


26 cancer patients (types unspecified) with a Brief Fatigue Inventory (BFI) score of at least 4*

- After completing a four-week course of oral modafinil (100 mg daily for two weeks, followed by 200 mg daily for an additional two weeks), patients showed no significant change in performance on the following neurocognitive tests: the Hopkins Verbal Learning Test (HVLT), the Grooved Pegboard Test, the Controlled Oral Word Association Test (COWAT) and the Trail Making Test A.

Berenson et al.‎‎ [115]

Double-blind, placebo controlled phase three trial


Multiple myeloma patients (n = 35) with moderate CRF*

- Patient receiving oral modafinil (150 mg daily for 56 days) showed no significant improvement compared to placebo in three objective measures of cognitive function (the Trail Making Test-version B, the Symbols Digits Modality Test and the digit span test)

Escalante et al.‎‎ [117]

Randomized, double blind, placebo-controlled crossover trial


BC patients (n = 38), 35 (92.1%) of which were undergoing chemotherapy or chemotherapy + ET treatment during the study period

- Methylphenidate-treated patients (18 mg/day for two weeks) performed significantly better than placebo in the Wechsler Adult Intelligence Scale Digit Span Test (p = 0.001), indicating improved cognitive processing speed.