Impairment of Cognitive Function in Women Receiving Adjuvant Treatment for High-Risk Breast Cancer: High-Dose Versus Standard-Dose Chemotherapy

Dam, F.S.A.M. van; Schagen, Sanne B.; Müller, Martin; Boogerd, Willem; Wall, Elsken van der; Fortuyn, M.E. Droogleever; Rodenhuis, S.

doi:10.1093/jnci/90.3.210

Cited by 694 publications

(522 citation statements)

References 27 publications

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“…A second long-term toxicity that we have recently described is impairment of cognitive function (van Dam et al, 1998). This type of toxicity has been associated with a single high-dose course CTC and many of the patients reported here have contributed to these studies (Schagen et al, 2001).…”

Section: Discussionmentioning

confidence: 61%

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience

et al. 2003

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High-dose chemotherapy (HD-CT) has a role in the potentially curative treatment of several tumours. The relative efficacies of the different regimens have not been studied in comparative trials, but it is clear that toxicities differ significantly between them. We analysed the immediate and long-term toxicity in the first 100 consecutive patients treated with the CTC regimen (cyclophosphamide 6000 mg m À2 , carboplatin 1600 mg m À2 (or 20 mg ml À1 min under the curve (AUC)) both as daily 1 h infusion, thiotepa 480 mg m À2 as twice daily 30 min infusion, all divided over 4 consecutive days) followed by peripheral blood progenitor cell reinfusion (PBPC-Tx). Most patients had high-risk (n ¼ 86) or metastatic (n ¼ 4) breast cancer, or a germ cell tumour (n ¼ 8). Two patients (with a medulloblastoma and an aesthesioneuroblastoma, respectively) received CTC as off-protocol salvage regimen. The main toxicity was bone marrow suppression. Most patients had PBPC-Tx with granulocyte colony-stimulating factor (G-CSF), and the median time to neutrophil count 500 Â 10 6 l À1 and platelet count 420 Â 10 9 l À1 without transfusion independence was 10 (range 8 -25) and 13 (8 -60) days, respectively. The toxic death rate was 1%. Other frequent toxicities were neutropenic fever requiring antibiotics (n ¼ 65), central catheter-related infection (n ¼ 12) or a bleeding episode (n ¼ 48), mostly epistaxis (n ¼ 26). Reversible cardiac toxicity was seen in six patients and pulmonary events occurred in seven patients (infection (n ¼ 6), embolism (n ¼ 1)). Grade 3 -4 gastrointestinal toxicity was frequent: nausea and vomiting 55%, diarrhoea 28% and mild liver toxicity (transaminase elevations) 9%. One patient pretreated with cisplatin had a kidney transplantation 8 years after HD-CT. Late complications included reversible radiation pneumonitis (n ¼ 12) and chronic heart failure (n ¼ 2). We found five second solid malignancies and two myelodysplasias. In conclusion, the CTC regimen is associated with a moderate, mainly reversible, toxicity. Future studies need to compare the efficacy and toxicity of the different HD-CT regimens.

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Section: Discussionmentioning

confidence: 61%

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience

et al. 2003

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“…The 95th percentile of the healthy controls was used as a cutoff score for cognitive disability. 25 The application of this algorithm to our data showed that a glioma patient was judged to have a cognitive disability if he or she had deviant scores for at least four of the 20 tests. Only tests for which healthy controls could be individually matched with low-grade glioma patients for age, sex, and educational level were used for this analysis.…”

Section: Study Measuresmentioning

confidence: 90%

“…29 We saw a somewhat stronger relation between objective test results and self-reported cognitive function than that noted in earlier studies of patients with brain tumours and those with systemic cancer. 25,30 Cull and colleagues 17 suggested that cognitive complaints of cancer patients might actually indicate feelings of anxiety, depression, or fatigue. Moreover, a dissociation between objective cognitive test results and self-reported cognitive function holds true especially for patients with brain cancer whose judgment could be severely impaired by the tumour.…”

Section: Patient Groupsmentioning

confidence: 99%

Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study

Klein¹,

Heimans²,

Aaronson³

et al. 2002

The Lancet

562

343

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“…Cyclophosphamide; Doxorubicin; Chemotherapy; Learning; Rat A growing body of evidence indicates that cancer chemotherapy results in cognitive changes during treatment, immediately post-treatment, and up to 10 years following therapy [2,4,15,21,25,32]. The cognitive deficits that are experienced are diverse and vary in severity; however, problems with memory function and executive processes are the most…”

Section: Introductionmentioning

confidence: 99%

Cancer chemotherapy impairs contextual but not cue-specific fear memory

MacLeod

DeLeo²,

Hickey³

et al. 2007

Behavioural Brain Research

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This study examined the effects of a standard breast cancer chemotherapeutic protocol on learning and memory in rats. Ovariectomized rats were treated once a week for 3 weeks with a combination of cyclophosphamide and doxorubicin prior to training in a classical fear conditioning task. Training took place 1 week after the final treatment. During the training session, an auditory stimulus (a tone) was paired with a mild foot-shock. The resulting conditioned fear to the tone (cue-specific fear) and to the training environment (contextual fear) was measured in subsequent test sessions. Chemotherapy did not affect the acquisition of the conditioned response (freezing) during the training session or the expression of fear during the tone test session. In contrast, rats treated with cyclophosphamide and doxorubicin exhibited decreased freezing during the context test session, suggestive of a specific deficit in hippocampal-related learning and memory. Together, these data indicate that administration of cyclophosphamide and doxorubicin may have toxic effects on the hippocampus and results in specific learning deficits shortly after treatment has ended. KeywordsCyclophosphamide; Doxorubicin; Chemotherapy; Learning; Rat A growing body of evidence indicates that cancer chemotherapy results in cognitive changes during treatment, immediately post-treatment, and up to 10 years following therapy [2,4,15,21,25,32]. The cognitive deficits that are experienced are diverse and vary in severity; however, problems with memory function and executive processes are the most

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Impairment of Cognitive Function in Women Receiving Adjuvant Treatment for High-Risk Breast Cancer: High-Dose Versus Standard-Dose Chemotherapy

Abstract: High-dose chemotherapy appears to impair cognitive functioning more than standard-dose chemotherapy. Central nervous system toxicity may be a dose-limiting factor in high-dose chemotherapy regimens.

Cited by 694 publications

References 27 publications

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience

Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study

Cancer chemotherapy impairs contextual but not cue-specific fear memory

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