Anticipatory Nausea and Vomiting in Cancer Patients Undergoing Chemotherapy Treatment: Prevalence, Etiology, and Behavioral Interventions

Nausea and vomiting are comrrwn side effects thut occur after chemotherapeutic drugs are given to treat cancer. Recent attention has been focused on the occurrence of nausea and vomiting in anticipation of a treatment. Prevalence data from a variety of studies show that approximately 25 70 of patients receiving chemotherapy treatments for calzcer develop anticipatory nausea and vomiting (ANY by the time of their fourth treatment. A review of studies examining models and variables associated with potential etiology indicates that no single demographic, clinical, or psychologic characteristic appears to be as related to the development of anticipatory side effects as are several characteristics in concert. Spectfically, patients under 50 years of age who are treated with potentially emetic chemotherapy and who experience distressing nausea and vomiting after treatment appear to be at risk for the development of anticipatory nausea and vomiting. The development of anticipatory side effects a@ ears to follow a classically conditioned model; no compelling data contradict a view that anticipatory side eff t ec s are learned. A review of both case and controlled studies on the biobehauioral treatment of ANV indicates that: (a) while studies on Hypnosis have been methodologically weak, they provide support for continued controlled inuestigations in children; (b) P ro g ressive Relaxation Training appears effective in controlling posttreatment nausea and vomiting; and (c) Systematic Desensitization appears effectiue in controlling both anticipatory and posttreatment nausea and vomiting. The review concludes with a brief consideration of several methodologic and practical issues thut point to promising directions for future research in the area. This research was supported by a Research Career Development Award K04-CA-01038, by research grants CA11198 and CA26832 from the National Cancer Institute, and by research grants PDT 2 17 and CH 35 1A from the American Cancer Society. Request for reprints should be sent to Gary R. Morrow Ph.D., Associate Professor of Oncology in Psychiatry (Psychology), Department of Psychiatry, University of Rochester School of Medicine and Dentistry, 300 Crittenden Blvd., Rochester, NY 14642. 517 518 G. R. Morrow and P L. Dobkin The most common side effects of chemotherapy drug treatment for cancer are nausea and vomiting. If not adequately controlled, nausea and vomiting can lead to further complications, such as anorexia and metabolite imbalance, along with contributing to a general deterioration of the cancer patient’s psychological and physical condition. Cancer patients may develop as much apprehension and dread about treatment and its side effects as they do about their disease. Many cancer patients treated with chemotherapy drugs request dosage reductions or even terminate potentially curative treatment regimens prematurely due to poorly controlled nausea and vomiting (Holland, 1977; Hoagland, Morrow, Bennett, & Carnrike, 1983). In addition to becoming nauseous and/or vomiting following chemotherapy treatment, a number of patients experience these aversive side effects prior to a treatment session (Morrow, 1981, 1982, 1986a). Increasing experimental attention is being paid to this phenomenon referred to as anticipatory nausea and vomiting (ANV), for it is a side effect that appears to link psychological, neurological, and physiological systems.’ In addition, anticipatory side effects may provide an unusual opportunity to study the natural occurrence of what appears to be a form of aversive learning in humans (Burish & Carey, 1986). Here we examine and critique studies on the prevalence, etiology, and treatment of anticipatory nausea and vomiting, with a view toward organizing past research to identify further directions for exploration. PREVALENCE OF ANTICIPATORY NAUSEA AND VOMITING Since 1979 at least 28 studies (summarized in Table 1) have reported the prevalence of anticipatory nausea and vomiting in adult and pediatric cancer chemotherapy patients. As shown at the bottom of the table, a range of prevalence rates of anticipatory nausea and vomiting have been reported in the different studies. On the lower end of estimates, rates of anticipatory side effects of 18% of 71 ‘To appreciate how psychological and biobehavioral effects may influence the physiologic response of nausea and vomiting, it may be helpful to briefly review the physiology of these side effects. The final common pathway for the coordination of the respiratory muscles and other structures involved in the act of vomiting and probably also the sensation of nausea is an area of the dorsolateral reticular formation of the medulla called the vomiting center (Borison & Wang, 1953). There are at least three major inputs to this structure. Although the mechanisms by which nausea and vomiting occur during chemotherapy treatment are not totally characterized (Lazlo, 1983), there is an emerging consensus that at least three major inputs are involved. The first is from the vestibular system. This is thought to be involved in the development and expression of nausea and vomiting due to motion (Reason & Brand, 1975). A second input is the area postrema (Borison, Hawken, Hubbard, & Sirett, 1975). This is an area near the fourth ventricle that is in the unique position of being in contact with both cerebral spinal fluid and blood. It is thought to be that area in which nausea and vomiting due to chemical challenges, such as food poisoning, toxicity, and nausea attributable to chemotherapy drugs takes place. The final large input are cortical areas from the limbic system and the cerebrum. There are fiber tracts from areas in the limbic system associated with the expression of emotion and associated with memory that connect to the vomiting center. This provides a neurologic substrate which makes possible the involvement of psychologic phenomenon in the expression of nausea/vomiting. Anticipatory Nausea and Vomiting 519 TABLE 1. Prevalence of Anticipatory Side Effects in Cancer Chemotherapy Patients Authors Anticipatory Number Anticipatory Anticipatory nausea and/or studied nausea vomiting vomiting Andrykowski (1987) Andrykowski et al. (1985) Andrykowski et al. (1987) Cella et al. (1984) Cohen (1982) Dobkin et al. (1985) Dolgan et al. (1986) Fdez-Arguelles et al. (1985) Fetting et al. (1983) Jacobsen et al. (1985) Ingle et al. (1984) Love et al. (1983) Morrow (in press) Morrow et al. (1982) Morrow & Dobkin (1985) Nesse et al. (1980) Nerenz et al. (1986) Nicholas (1982) Nicholas (1983) Olafsdottir et al. (1986) Palmer et al. (1980) Schultz (1980) Scogna & Smalley (1979) van Komen & Redd (1985) Weddington (1982) Weddington et al. (1984) Wilcox et al. (1982) Wilson (1986) Total Median Range 78 71 77 60 149 125 80 72 123 27 60 126 406 225 736* 18 61 71 50 50 24 68 41 100 17 50 52 66 2,452 80 17-736 33% 37% 57% 63% 42% 32% 29% 14% 57% 38% 24% 26% 44% 24% 42% 40% 22% 33% 53% 20% 18 33% 14-63% 27% 12% 20% 9% 8% 14% 9% 11% 12% 33% 8% 10 12% 9-27% 31% 31% 25% 38% 21% 18% 31% 37% 38% 9