Anticipatory nausea in cancer patients receiving chemotherapy: Classical conditioning etiology and therapeutical implications

Abstract

The delivery of cytotoxic drugs in cancer treatment is often accompanied by posttreatment side effects (e.g., nausea). Moreover, there is evidence that cancer patients are at risk to develop these side effects in anticipation of chemotherapy (i.e., anticipatory nausea [AN]). AN can be explained as the result of a classical conditioning process with the cytotoxic drug as the unconditioned stimulus (US). Stimuli paired with the US (e.g., smells, tastes) can become conditioned stimuli (CSs) eliciting AN as the conditioned response (CR). The present study was conducted to test whether AN shows characteristics of a CR. Fifty-five ambulatory cancer patients were asked to record nine kinds of physical symptoms (e.g., nausea, vomiting, sweating) on time-scheduled symptom lists: after an infusion (indicating posttreatment symptoms) and prior to their next infusion (indicating anticipatory symptoms). Each measurement period covered a maximum of 48 hours. AN was reported by ten patients (18.08%). Data revealed (a) a statistically significant association between posttreatment nausea and vomiting, respectively, and AN; (b) the occurrence of AN increased with drug emetogenity (i.e., US-intensity); and (c) the duration of AN increased with temporal proximity to the infusion. The results support the conditioning model. Thus, it is proposed to prevent AN by classical conditioning techniques (e.g., overshadowing).

Role of classical conditioning in learning gastrointestinal symptoms

“…AN was reported by 18.1% of the patients and, in correspondence with the conditioning predictions, there was a statistically significant association between the occurrence of post-treatment nausea (PN) and AN, and post-treatment vomiting (PV) and AN (i.e., occurrence of the UR and the CR), and between AN and the degree of emetogenity of the drug previously experienced (US-intensity). Furthermore, the duration of reported AN increased as temporal proximity to scheduled infusion onset increased [41] . Similar results [18] were obtained in a study with pediatric cancer patients (M = 10.1 ± 0.9 years), with a preexperience of 6.1 ± 0.5 previous cycles of chemotherapy.…”

“…In the first correlative study [41] , 55 ambulatory adult cancer patients [mean age: 50.78 ± (SEM) 2.03 years] with a mean preexperience of 9.8 ± 0.96 infusions, were asked to record nine symptoms (nausea, vomiting, dizziness, sweating, hot flashes, heartburn, headache, weakness, and heartbeat) after an infusion to assess post treatment symptoms and prior to a subsequent infusion (to assess anticipatory symptoms). Each measurement period (posttreatment and anticipatory) covered a maximum of 48 h, divided into four 12-h periods of days (6 am to 6 pm) and nights (6 pm to 6 am).…”

Factors of Anticipatory Nausea and Vomiting in Cancer Patients

“…Second, clinical factors involve chemotherapy (Pickett, 1991;De Mulder, 1992;Fetting et al, 1983;Stockhorst et al, 1993;, Blasco, 1994;Rhodes, 1986;Alba et al, 1989;Andrykowiski et al, 1985;Stefanek et al, 1988;Nesse et al, 1980), chemotherapy cycle (Watson et al, 1998;Morrow and Rosenthal, 1996;Blasco, 1994;Coons et al, 1987;Alba et al, 1989;Andrykowiski et al, 1985;Love et al, 1983;Nesse et al, 1980), anti-emetic agents (Blasco, 1994) and stage of disease (Pickett, 1991;Love et al, 1983;Blasco, 1994;Love et al, 1983;Nesse et al, 1980). Third are physical symptoms Pickett, 1991;Nerenz et al, 1982;Rhodes, 1986;Sandra et al, 1992;Duigon, 1986).…”

“…Fourth, emotional status such as anxiety Boakes, et al, 1993;Coons et al, 1987;Altmaier et al, 1982;Watson et al, 1998;Blasco, 1994;Love et al, 1983;Rhodes, 1986;Sandra et al, 1992;Ingle et al, 1984;Andrykowiski et al, 1985;Nesse et al, 1980;Duigon, 1986), depression (Blasco, 1994;Ingle et al, 1984;Altmaier et al, 1982), emotional disorder (Nerenz et al, 1982), stress and coping (Altmaier et al, 1982;Pickett, 1991;Blasco, 1994;Ingle et al, 1984). Fifth, post -chemotherapy nausea and vomiting Matteson et al, 2002;Burish and Carey, 1986;Stockhorst et al, 1993;Blasco, 1993;Sandra et al, 1992;Alba et al, 1989;Ingle et al, 1984;Andrykowiski et al, 1985;Stefanek et al, 1988) and therapy experience (Watson et al, 1998;Matteson et al, 2002;Coons et al, 1987;De Mulder, 1992;Altmaier et al, 1982;Fetting et al, 1983;Blasco, 1994) be caused. Sixth, environmental factors are odor (Boakes et al, 1993), taste, smelling and seeing (Nerenz et al, 1982;Love et al, 1983;Blasco, 1994;Nesse et al, 1980), sensor...…”

“…Fifth, post -chemotherapy nausea and vomiting Matteson et al, 2002;Burish and Carey, 1986;Stockhorst et al, 1993;Blasco, 1993;Sandra et al, 1992;Alba et al, 1989;Ingle et al, 1984;Andrykowiski et al, 1985;Stefanek et al, 1988) and therapy experience (Watson et al, 1998;Matteson et al, 2002;Coons et al, 1987;De Mulder, 1992;Altmaier et al, 1982;Fetting et al, 1983;Blasco, 1994) be caused. Sixth, environmental factors are odor (Boakes et al, 1993), taste, smelling and seeing (Nerenz et al, 1982;Love et al, 1983;Blasco, 1994;Nesse et al, 1980), sensory stimli (Fetting et al, 1983;Duigon, 1986;Stefanek et al, 1988), seeing the syringe (Nerenz et al, 1982) and difficulty of venipunture (Coons et al, 1987), Finally, a lot of studies explained that ANV is conditioning process (Kvale et al, 1994;Stockhorst et al, 1993;Pickett, 1991;Coons et al, 1987;Blasco, 1994;Alba et al, 1989;Duigon, 1986;Stefanek et al, 1988).…”