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Palliative and supportive care highlights from the ASCO Annual Meeting
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At the 2008 ASCO Annual Meeting, there were several clinical science symposia and poster sessions about the topics of palliative and supportive care. Here are some highlights from those presentations and posters.
Data were reported from two large phase-3, double blind, randomized control trials using the NK-1 inhibitor casopitant in moderate and highly emetogenic chemotherapy in addition to the 5HT3 inhibitor and steroids.
Strausz et al reported the findings from a phase-3 study of casopitant in highly emetogenic chemotherapy regimens. More than 99% of the 810 patients in this trial were assigned cisplatin-based therapy for up to six cycles. The control arm was assigned ondansetron (32 mg IV on day one) and oral dexamethasone (12 mg on day one, 8 mg twice a day on days two through four) with placebo. The intervention arm with one day of casopitant was assigned 150 mg oral casopitant on day one in addition to 32 mg IV ondansetron and 12 mg oral dexamethasone both on day one. The three day IV/oral intervention group was assigned 90 mg IV casopitant, 32 mg IV ondansetron and 12 mg oral dexamethasone on day one and 50 mg casopitant on days two through three, plus 8 mg oral dexamethasone twice daily on days two through four.
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The primary endpoint was complete response defined as no vomiting, retching or rescue medication use in the first 120 hours. The researchers reported a statistically significant improvement in control of symptoms with the use of a three-day IV/oral regimen with complete response rates ranging from 66% to 80%. The benefit was mainly in the delayed emesis, defined as hours 24 to 120. There were no significant toxicities reported with casopitant.
Grunberg et al reported results of a similar multinational, double blind, randomized placebo-controlled trial of casopitant for moderately emetogenic chemotherapy. In this trial, 1,933 patients receiving anthracycline- and cyclophosphamide-based chemotherapy were randomly assigned to one of four groups. All patients received oral ondansetron 8 mg twice daily on days one to three and 8 mg IV dexamethasone on day one. The control group received a placebo for three days. The second group was assigned 150 mg oral casopitant given on day one. The third group was assigned 150 mg oral casopitant on day one, plus 50 mg oral casopitant on days two to three. The fourth group was assigned 90 mg IV casopitant on day one and 50 mg oral casopitant on days two to three.
All of the intervention groups showed an improved complete response, which was mostly delayed (defined as 24 to 120 hours). These findings were maintained throughout the four cycles of chemotherapy administration. Interestingly, the group that received casopitant on day one only had similar benefit compared with three days of casopitant.
Thus, casopitant showed an improved control of emesis in moderately and highly emetogenic chemotherapies. Only one dose may be sufficient in the moderately emetogenic regimen. The control arm in the trial conducted by Grunberg et al is curious for the dexamethasone use for three days per cycle. We await the full description of these findings. Casopitant may become another tool in the armamentarium in prevention of chemotherapy-induced nausea and vomiting.
Fatigue is complicated
Fatigue is a common and difficult-to-treat symptom in patients with cancer and those undergoing treatment for cancer. Researchers studying fatigue at the University of Rochester reported on several findings from their study in a community setting. First, Mustian et al reported that cancer-related fatigue interferes with a patient’s ability to perform activities of daily living while receiving chemotherapy. This sets up the stage for the need to better understand and manage this potentially debilitating symptom.
Morrow et al reported results of a large phase-3 study of modafinil for sleep in patients with fatigue. The researchers reported that modafinil may improve sleep in those patients starting with severe fatigue. The results were not convincing and require additional work. There was no impact on depression in these patients. A similar study, conducted by the same group, had previously reported that, with the use of an antidepressant, the depressive symptoms had improved but the sleep disturbance had not.
This leads to several questions of whether these symptoms are related or occur in a cluster, and if they do, is there a related pathophysiology? Also, are we targeting the symptoms or the pathophysiology of the symptoms? The implications of related pathophysiology are important for better understanding of these symptoms and treatment. At a recent annual meeting of Multinational Association of Supportive Care in Cancer (MASCC) in Houston, Stephen Sonis, DMD, advocated that we should examine these symptom clusters more carefully to better understand their potential pathophysiology and develop interventions that target the pathophysiology in addition to the symptoms.
Researchers have noted that several of the symptoms occur together, or in a “cluster.” In a report from the 2002 National Institutes of Health State of the Science Conference on Symptom Management in Cancer, symptom clusters were defined as three or more symptoms that are related to each other. Sriram Yennurajalingam, MD, from The University of Texas M.D. Anderson Cancer Center, reported on a possible clustering of fatigue, drowsiness, sleep and well-being. Others have reported depression as part of a fatigue cluster as well.
Genomics in symptom management
With the development in genomics in the treatment of patients with cancer, attention needs to be paid to the impact of genomics on symptoms and toxicities caused by the cancer and cancer treatment as well as the treatment of these symptoms and toxicities. Reyes-Gibby et al explored the effects of single nucleotide peptide variants of cytokine genes (tumor necrosis factor–alpha, interleukin-6 and IL-8) on variability of self-reported pain and response to morphine in patients with lung cancer. One hundred forty patients from another large registration trial were referred to palliative care during their disease trajectory. The researchers reported that specific polymorphisms in TNF and IL-6 were associated with pain severity and requirement of morphine doses. This may be the beginning of understanding the biology of symptoms and toxicities and may change practice in the future.
Revisiting internal medicine basics
With the advent of newer agents, newer toxicities have surfaced, including several common medical problems such as skin rashes, hypertension, hypercholesterolemia and disturbance of glucose metabolism. Prevention of the long-term complications of these toxicities will become more important as we use these agents in curative regimens and earlier in disease trajectory. Prevention of short-term complications of these drugs is important in treating patients with comorbid conditions such as heart disease. As we learn more about these new drugs, oncologists may have to get a refresher course in the newer treatment guidelines for common medical problems such as hypertension and diabetes and work with patients’ internists more closely.
For more information:
- Grunberg SM. #9540.
- Mustian KM. #9500.
- Reyes-Gibby CC. #9503.
- Straustz J. #20585. All presented at: 2008 ASCO Annual Meeting; May 30-June 3, 2008; Chicago.