Patients treated with chemotherapy have disturbed sleep-wake activity, a prospective study from Hong Kong and Australia confirms.
“The first administration of adjuvant chemotherapy is associated with sleep disturbance and sleep-wake activity rhythm disruption among breast cancer patients, while the disturbance and disruption during the last cycle are less severe,” the researchers write in Sleep, online December 14.
“Nevertheless, repeated administration of chemotherapy results in progressive impairment of nocturnal melatonin production,” they add.
Dr. Lap Ah Tse of the Jockey Club School of Public Health and Primary Care of the Chinese University of Hong Kong and colleagues investigated the patterns of sleep, sleep-wake activity rhythm, and first morning void urinary melatonin levels in 180 patients undergoing adjuvant chemotherapy for stage I-III primary breast cancer.
At baseline, the median participant age was 53, and most were married with high school or higher education; 76% reported sleep disturbance (Pittsburgh Sleep Quality Index (PSQI) 5 or higher); 85% had good performance status; and 72% had undergone mastectomy.
Guided by their disease condition and preference, patients received one of three adjuvant chemotherapy regimens: six cycles of FEC-T (5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel; 44% received this), four cycles of doxorubicin plus cyclophosphamide (29%), or four cycles of docetaxel plus cyclophosphamide (27%).
Participants completed a baseline questionnaire about sociodemographics and lifestyle, including age, education level, family income, marital status, and drinking history; they completed the PSQI to evaluate their subjective sleep quality; and the researchers reviewed their medical records.
The patients wore wrist actigraph monitors GENEActiv Original (Activinsights Company, UK) on the non-dominant hand for a week before chemotherapy, and during the first week of the first cycle. Afterwards, those treated with doxorubicin plus cyclophosphamide or with docetaxel plus cyclophosphamide wore the monitor during the first week of the fourth cycle (end of chemotherapy), and those on FEC-T wore the monitor during the first week of the third cycle (end of FEC). They collected their first morning void urine samples before treatment as well as during their first and the last cycle.
The actigraphy data were extracted to determine sleep efficiency, sleep duration, total nighttime wake time, percent rhythm, F-statistic, amplitude, mesor, and acrophase.
Researchers also assessed urinary 6-sulfatoxymelatonin (aMT6s) levels.
Linear mixed-effects models were used to calculate the changes in actigraphy values as well as first morning urinary aMT6s before and during chemotherapy, and univariable and multivariable models were used for all actigraphy values and urinary aMT6s. The multivariable linear mixed-effects models were adjusted for cancer stage; age; body mass index; menopausal status; performance status; surgery type; comorbidities; corticosteroid use; sociodemographics; alcohol consumption; and chemotherapy.
Compared with baseline, sleep efficiency during the first and last cycle decreased by 10% and 5%, respectively; rhythm decreased by 27% during the first cycle and 21% during the last cycle; and during the first and last cycles, aMT6s levels decreased by 11% and 15%, respectively, compared to baseline.
“This study provides the first epidemiological evidence that nocturnal melatonin secretion is progressively impaired over the course of chemotherapy in breast cancer patients receiving chemotherapy,” the authors write.
The authors note that disturbed sleep with weak sleep-wake activity rhythm is a common problem among breast cancer survivors who have chemotherapy.
“This longitudinal study suggests that sleep, sleep-wake activity rhythm, and nocturnal melatonin production are rapidly disrupted after the administration of the first cycle of adjuvant chemotherapy in breast cancer patients,” they write.
“Sleep disturbance is associated with poor quality of life, fatigue, and depression in breast cancer patients. Weak sleep-wake activity rhythm is evident to be a prognostic risk factor associated with poor survival of cancer patients and the side effects of anti-cancer treatment,” they add. “Furthermore, disruptions in sleep and sleep-wake activity rhythm may disrupt the production of nocturnal melatonin, which is an endogenous hormone playing a pivotal role in alleviating oxidative stress and regulating the immune and hematological system.”