Advertisement
help button home button The Oncologist
HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow eLetters: Submit a response to this article
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints/Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Spector, J. I.
Right arrow Articles by Creed, M. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Spector, J. I.
Right arrow Articles by Creed, M. R.
The Oncologist, Vol. 3, No. 6, 432-438, December 1998
© 1998 AlphaMed Press

Original Papers

A Comparison of Oral Ondansetron and Intravenous Granisetron for the Prevention of Nausea and Emesis Associated with Cisplatin-Based Chemotherapy

Jesse I. Spectora, Eric P. Lesterb, Eric M. Chevlenc, David Sciortinod, Jim H. Harveye, William Whaleyf, Stefan Madajewiczg, Randi Isaacsh, Howard D. Homesleyi, Sharon Yeej, Thomas M. Beckk, N. Simon Tchekmedyianl, Karen H. Crawfordm, Michael Amesm, Mary R. Creed, on behalf of the S3AA3004 and S3AA3007 Study Groupm

a Berkshire Hematology/Oncology, PC, Pittsfield, Massachusetts; b Lakeland Medical Center, St. Joseph, Michigan; c St. Elizabeth Hospital, Youngstown, Ohio; d Fort Wayne Medical Oncology/Hematology Inc., Fort Wayne, Indiana; e SORRA Research Center, Inc., Birmingham, labama; f West Paces Clinical Research, Atlanta, Georgia; g University Medical Center, Stony Brook, New York; h Northern New Jersey Cancer Center, Hackensack, New Jersey; i Carolina Gynecological Oncology, Winston-Salem, North Carolina; j Arcadia, California; k Mountain States Tumor Institute, Boise, Idaho; l Pacific Shores Medical Group, Long Beach, California; m Glaxo Wellcome Inc., Research Triangle Park, North Carolina, USA

Correspondence: Mary R. Creed, M.S.N., Glaxo Wellcome Inc., Five Moore Drive, P.O. Box 13398, Research Triangle Park, North Carolina 27709-3398, USA. Telephone: 919-483-5196; Fax: 919-483-0103; e-mail: mrc7253{at}glaxowellcome.com


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 Conclusion
 References
 
Purpose: To compare the efficacy and safety of oral ondansetron with i.v. granisetron each given as a single dose prior to administration of highly emetogenic cisplatin chemotherapy.

Patients and Methods: Chemotherapy-naive patients with histologically confirmed malignancies were randomized to receive a single 24 mg ondansetron hydrochloride tablet plus a 50 ml i.v. infusion of normal saline, or a single 10 µg/kg (50 ml) i.v. infusion of granisetron plus a placebo tablet in this multicenter, double-blind, parallel-group trial. Study drug was administered 30 min prior to a single i.v. infusion of cisplatin (50-75 mg/m2), given over a period of <= three h. Concurrent administration of corticosteroids was not allowed. Efficacy measurements included the number of emetic episodes, need for rescue medication, and patient assessments of nausea and appetite. Complete response (CR) was defined as no emetic episodes, rescue, or withdrawal; major response was defined as one or two episodes. Safety was evaluated by monitoring adverse events and changes in laboratory parameters.

Results: A total of 371 patients entered the study and received study drug, of whom 184 received ondansetron and 187 received granisetron. For all parameters tested, a single 24 mg oral ondansetron tablet was at least as effective as i.v. granisetron. CR was achieved in 58% of ondansetron-treated patients and 51% of granisetron-treated patients (95% confidence interval on the difference: -4% to 17%). Subjective assessments revealed no difference with regard to complete control of nausea, appetite, or satisfaction with antiemetic therapy. Both drugs were well tolerated; the most common adverse event was headache.

Conclusion: A single 24 mg oral dose of ondansetron is at least as safe and effective as a single i.v. infusion of 10 µg/kg of granisetron in preventing nausea and vomiting induced by highly emetogenic cisplatin chemotherapy.

Key Words. Cisplatin • Chemotherapy • Antiemetics • Ondansetron • Granisetron • Vomiting • Nausea


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 Conclusion
 References
 
Highly emetogenic chemotherapeutic agents, including cisplatin, are widely used in treating malignant disease. Nausea and vomiting are the most frequently occurring side effects of therapy with these agents. Although the extent of nausea and vomiting varies by chemotherapeutic regimen, more than 90% of patients who receive >= 50 mg/m2 of cisplatin will vomit during the first 24 h after administration unless they receive effective prophylactic antiemetic therapy [1]. Failure to control these sequelae negatively affects patients' quality of life and may result in reluctance to continue potentially beneficial treatment [2, 3].

Physiologically, serotonin and 5-HT3 receptors play key roles in the induction of nausea and vomiting by chemotherapeutic agents [4-7]. Ondansetron is a selective 5-HT3 receptor antagonist highly effective in controlling nausea and vomiting in a variety of clinical situations. Additionally, numerous studies investigating the use of ondansetron and granisetron, another 5-HT3 receptor antagonist, have shown that when delivered intravenously both drugs are safe and highly effective in preventing nausea and vomiting induced by moderately high or highly emetogenic chemotherapy [4, 8-15]. Studies have also been conducted which demonstrate similar efficacy results with oral granisetron 2 mg and i.v. ondansetron 32 mg in patients receiving moderately to highly emetogenic chemotherapy [16, 17]. Although oral ondansetron at doses of 8 mg TID and 8 mg BID has been proven effective for use in moderately emetogenic chemotherapy, the optimal oral ondansetron dose and regimen for patients receiving highly emetogenic chemotherapy has not been clearly defined.

A single oral dose of ondansetron 24 mg was chosen for investigation in this study. It was theorized that having the most ondansetron available to interact with the 5-HT3 receptors at the time of maximal release of serotonin, 2 to 6 h following cisplatin administration [8], would provide the greatest antiemetic efficacy. Beck et al. [18] demonstrated that a single 32 mg i.v. dose of ondansetron prior to the administration of cisplatin was as effective as, if not superior to, the continuous infusion and intermittent dosing regimens used in earlier studies. Using this same logic, the approved 1994 oral dosing regimen of ondansetron (8 mg TID) effective in moderately emetogenic chemotherapy regimens was combined into a single oral dose (24 mg) to be administered prior to a cisplatin-based chemotherapy regimen.

This study was designed to compare the antiemetic efficacy and safety of ondansetron administered as a single 24 mg tablet with a single infusion of granisetron 10 µg/kg in patients receiving highly emetogenic cisplatin chemotherapy (cisplatin 50-75 mg/m2). Although numerous reports in the literature state that the use of dexamethasone adds to the efficacy of the 5-HT3 receptor antagonists, corticosteroids (including dexamethasone) were excluded from the study in order to demonstrate the antiemetic activity of a single oral dose of ondansetron and a single i.v. dose of granisetron in patients receiving highly emetogenic cancer chemotherapy.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 Conclusion
 References
 
Patient Selection
Two identically designed multicenter, randomized, double-blind, parallel-group studies were conducted. Chemotherapy-naive male or female patients, age 12 years or older, with histologically confirmed malignancy, scheduled to receive cisplatin 50-75 mg/m2 administered intravenously over a period of <= 3 h were eligible to participate. Females were eligible if surgically sterilized, post-menopausal, or pre-menopausal with a negative pregnancy test. Patients were excluded from the trial if they had a Karnofsky performance status of <60%; had received an investigational drug within the previous 30 days (or were scheduled to receive an investigational drug during the study); were scheduled to receive any additional highly emetogenic chemotherapeutic agents; had chronic nausea and/or vomiting, or experienced retching, vomiting, or uncontrolled nausea within 24 h prior to administration of the study drug. Medications with antiemetic properties were not allowed within 24 h prior to or during the study period. Patients could not undergo radiation therapy to the abdomen or pelvis within 48 h prior to or during the study period. The protocol was reviewed and approved by the Institutional Review Board at each study site and written informed consent obtained from each patient prior to the performance of any study-related procedures.

Chemotherapy
Eligible patients were to receive cisplatin at a dose of 50-75 mg/m2 administered over a period of <= three h as a single i.v. infusion. The protocol was amended after study initiation to allow use of carboplatin at a dose of >200 mg/m2 in place of cisplatin. Co-administration of other chemotherapeutic agents was permitted at the discretion of the investigator, with the exception of cyclophosphamide at a dose of >=500 mg/m2, nitrogen mustard, dacarbazine (DTIC), procarbazine, carmustine, and ifosfamide.

Antiemetic Treatment
Patients were randomized (1:1) in a double-blind fashion to receive either a single 24 mg ondansetron hydrochloride tablet (Zofran®, Glaxo Wellcome Inc.; Research Triangle Park, NC) and a 50 ml i.v. infusion of normal saline, or a single 10 µg/kg (50 ml) i.v. infusion of granisetron (Kytril®; SmithKline Beecham Pharmaceuticals; Philadelphia, PA) and a placebo tablet. The co-administration of corticosteroids, including dexamethasone, was not permitted. The administration of rescue antiemetic therapy was allowed at the discretion of the investigator if emetic symptoms were not controlled by the study drug.

Assessment of Antiemetic Efficacy and Safety
Efficacy data were collected for each patient for 24 h after the start of cisplatin administration. The primary efficacy variable was the number of patients with no emetic episodes who completed the trial without rescue medication (complete response [CR]). An emetic episode was defined as a single vomit or retch, or any number of continuous vomits and/or retches (i.e., two or more vomits and/or retches occurring within one minute of each other). Secondary efficacy parameters included the number of patients with therapeutic failures (i.e., more than five emetic episodes over the 24-h study period, the need for rescue therapy due to the severity of nausea or vomiting, or withdrawal from the study due to lack of efficacy); the number of patients with CR or major response (defined as one to two emetic episodes); time to first emetic episode, and withdrawal or rescue.

Subjective measures of efficacy included patient assessment of nausea, appetite, and satisfaction with antiemetic therapy. Patient assessment of nausea was performed using an 11-point linear numerical scale ranging from 0 (no nausea) to 10 (nausea as bad as it could be). Appetite was assessed using a 4-point scale categorized as "as usual," "better than usual," "worse than usual," and "not assessable" (i.e., unable to take anything by mouth). Patient satisfaction with antiemetic therapy was rated using a 5-point scale ranging from 1 (very satisfied) to 5 (very dissatisfied).

Safety evaluations were based on reports of adverse events (defined as any untoward medical occurrence) and laboratory data. Adverse events were monitored from the time of study drug administration up to 24.5 h post-administration. Adverse events considered by investigators to be potentially related to study drug were documented for up to eight days after study drug administration. Laboratory studies monitoring hematological parameters and blood chemistries including liver function tests were performed within seven days of the start of study drug administration and within eight days following the end of study drug administration. Any laboratory test results out of the normal range which were judged to be potentially drug related or clinically relevant were repeated and followed until return to normal or explained to the satisfaction of the investigator.

Statistical Methods
As the two studies were identical, data were combined and analyzed as a single trial. The planned sample size of 364 patients was sufficient to detect a 15% difference between groups at the nominal, two-sided, 0.05 level of significance and 80% power. The safety population consisted of all patients who received at least one dose of study medication. The intent-to-treat population comprised all patients in the safety population who received cisplatin or carboplatin chemotherapy and was used for all study endpoints.

The primary efficacy analysis compared the number of patients in each treatment group who experienced a CR during the post-treatment period. Patients who reported more than five emetic episodes, who were rescued with additional medications, or who were withdrawn due to lack of efficacy were assigned the same arbitrarily high value for the number of emetic episodes (i.e., >5) to designate therapeutic failure. The number of patients in each group with a complete or major response was also compared. These efficacy endpoints were analyzed using Mantel-Haenszel tests controlling for study site differences, with a 95% confidence interval for the difference in response rates between treatments computed using a large sample normal. Time to treatment failure (first emetic episode, rescue, or withdrawal) was assessed using Kaplan-Meier methods, and treatment groups were compared using log-rank tests. Nausea and appetite assessments were analyzed with overall scores compared between treatment groups using Mantel-Haenszel methods. Patient assessments of nausea, appetite, and patient satisfaction with antiemetic therapy made after a patient was withdrawn or rescued and any missing observations after a patient was withdrawn or rescued were replaced by the worst possible score (i.e., nausea = 10, appetite = worse than normal, patient satisfaction = very dissatisfied).


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 Conclusion
 References
 
Patient Disposition
A total of 371 patients entered the study and received study drug at 37 centers across the United States. Of these patients, 184 were randomized to ondansetron and 187 were randomized to granisetron.

Patient Characteristics
Treatment groups were similar with regard to demographic characteristics ( Table 1). The majority of patients were Caucasian (88% in the ondansetron group and 92% in the granisetron group). One patient in the granisetron group received carboplatin in place of cisplatin. Other cytotoxic agents were used in combination with cisplatin, including etoposide (49% in the ondansetron group and 47% in the granisetron group) and 5-fluorouracil (14% in the ondansetron group and 11% in the granisetron group). Combination chemotherapy regimens were similar between treatment groups. Lung cancer was the most common malignancy in both groups ( Table 1).


View this table:
[in this window]
[in a new window]
  		Table 1. Patient characteristics
 
Efficacy
Treatment response data are presented in Table 2. CR (no emetic episodes, rescue or withdrawal) was achieved in 58% of ondansetron-treated patients and 51% of granisetron-treated patients (95% confidence interval on the difference: -4% to 17%). The difference between the two treatment groups was not statistically significant. CR rates for both treatment groups showed that females were less likely to respond to antiemetic treatment than were males. In the ondansetron group, 46% of females versus 67% of males were CRs; in the granisetron group, 41% of females versus 59% of males were CRs. Therapeutic failure occurred in 27% of ondansetron-treated patients and in 35% of granisetron-treated patients. Similarly, 27% of ondansetron-treated patients and 34% of granisetron-treated patients received rescue medication. The proportion of patients experiencing CR plus major response was not statistically different between groups, occurring in 68% of ondansetron-treated patients and 61% of granisetron-treated patients ( Table 2). No statistically significant differences existed between treatment groups for time to treatment failure. Of those subjects who did fail treatment, few did so within the first 3 h; most did so between 6 and 24 h after the start of chemotherapy.


View this table:
[in this window]
[in a new window]
  		Table 2. Treatment response
 
Patient Assessments
Subjective patient responses regarding antiemetic efficacy were similar in both treatment groups and are listed in Table 3. Nausea assessments were not significantly different between treatment groups at any time point. The greatest difference between groups was noted at the 24-h assessment, when 10% more patients in the ondansetron group relative to the granisetron group reported no nausea (56% versus 46%, respectively). More ondansetron-treated patients (43%) completed the study without nausea, rescue, or withdrawal compared with granisetron-treated patients (35%), but this difference was not statistically significant. Post-treatment appetite assessments were not statistically significantly different between treatment groups ( Table 3). No statistically significant difference existed between treatment groups with regard to the number of patients who were satisfied with therapy. At 24 h 88% of patients in the ondansetron group were either "very satisfied" or "somewhat satisfied" with their therapy compared with 83% of the patients in the granisetron group.


View this table:
[in this window]
[in a new window]
  		Table 3. Antiemetic efficacy: patient response
 
Safety Assessments
All 371 patients who received study drug were included in the safety analyses. Adverse events reported during the study were similar between the two treatment groups. Twenty-four percent (24%) of patients in the ondansetron group and 28% of the patients in the granisetron group experienced one or more adverse events. The most common event was headache, reported in 7% of ondansetron-treated patients and 12% of granisetron-treated patients. Other adverse events, including diarrhea, constipation, malaise/fatigue, and fever, were similar between treatment groups and occurred in fewer than 5% of patients in either treatment group ( Table 4). The only adverse event occurring in 5% or more patients in either treatment group that was considered to be potentially drug related was headache (7% in the ondansetron group and 9% in the granisetron group). Analyses of pre-treatment and post-treatment laboratory values revealed similar changes between treatment groups in hematologic and clinical chemistry parameters, including hepatic enzymes. The majority of the transitions in laboratory values were within the normal range of the laboratory parameters evaluated and none of the changes were considered by investigators to be clinically significant.


View this table:
[in this window]
[in a new window]
  		Table 4 Safety
 

   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
Conclusion
 References
 
Recent changes in oncology practice and shifts in health care delivery have resulted in more patients being treated with highly emetogenic chemotherapeutic agents, including cisplatin, on an outpatient basis [19]. Consequently, oncology health care providers are forced to identify new and effective ways to provide high-quality patient care while containing costs. These changes pose unique challenges for the management of chemotherapy-associated symptoms such as nausea and vomiting. Single dose, oral antiemetic therapy that is proven safe and effective for highly emetogenic chemotherapy could provide a more convenient dosing regimen, improve antiemetic therapy compliance, reduce time of hospitalization or time spent in an outpatient treatment facility, and reduce administration costs.

Many significant improvements have been made in the past 10 years in the efficacy, safety, and ease of administration of antiemetic therapy used to control chemotherapy-induced nausea and vomiting. Serotonin receptor antagonists have been shown to be safe and effective, with corticosteroids reported to increase the rate of antiemetic control over that obtained with a 5-HT3 receptor antagonist alone [10, 19-22]. As a result, 5-HT3 antagonists in combination with corticosteroids are now the standard of care for moderately to highly emetogenic chemotherapy [23, 24]. However, in the current study co-administration of dexamethasone was not allowed so that the antiemetic efficacy of oral ondansetron 24 mg alone could be determined. Complete control of acute cisplatin-induced emesis in this study was achieved by 58% of patients who received oral ondansetron 24 mg as a single prophylactic antiemetic agent.

A recent study by Krazakowski et al. [25] evaluated single dose regimens of oral ondansetron 24 mg and i.v. ondansetron 8 mg in patients receiving cisplatin >=50 mg/m2 (median dose 75 mg/m2). Dexamethasone, 12 mg oral or 20 mg i.v., was included in the antiemetic treatment regimens. Complete control of emesis was obtained by 85% of patients in the oral group and 83% of patients in the i.v. group. No nausea was reported by 70% of patients in the oral group and 68% in the i.v. group. The results of this study support the use of a single 24 mg oral dose of ondansetron in patients receiving highly-emetogenic cisplatin chemotherapy and provide additional data on the additive antiemetic benefit of dexamethasone.

The present study demonstrates that a single 24 mg oral dose of ondansetron is as safe and effective in preventing nausea and vomiting induced by highly emetogenic cisplatin chemotherapy as a single i.v. infusion of 10 µg/kg of granisetron. An effective oral agent for highly emetogenic cisplatin chemotherapy offers improvements over i.v. therapy in terms of greater ease of administration, less time required by health care personnel, and reduction in overall health care expenses [26]. Furthermore, the use of oral antiemetics was approved by Medicare as part of the Balanced Budget Act of 1997 [27]. In order for a given oral antiemetic to be reimbursable by Medicare, the therapy must be: A) approved by the Food and Drug Administration for use in preventing nausea and vomiting associated with emetogenic chemotherapy; B) used as full replacement for the i.v. antiemetic that would have otherwise been administered at the time of chemotherapy; C) administered by the treating physician or in accordance with a written order from the physician as part of a cancer chemotherapy regimen, and D) administered with that particular chemotherapy regimen (i.e., initiated within 2 h of administration of chemotherapy and continued for no longer than 48 h from that time). Depending on the specifics of each clinical case, oral ondansetron potentially fulfills all of these criteria.


   Conclusion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 Conclusion
References
 
In conclusion, oral ondansetron 24 mg, when given as a single prophylactic dose prior to highly emetogenic cisplatin chemotherapy, is as safe and effective as i.v. granisetron. Oral ondansetron 24 mg provides the clinician a convenient dosing alternative and demonstrates a continuation of the proven efficacy and safety profile of ondansetron.


   Acknowledgments
 
This study was supported by a grant from Glaxo Wellcome Inc.

The S3AA3004 and S3AA3007 Study Group includes the authors and Norwood Anderson, M.D., New England Baptist Hospital, Boston, Massachusetts; Harinder Garewal, M.D., Tucson VA Medical Center, Tucson, Arizona; William J. John, M.D., Markey Cancer Center, Lexington, Kentucky; Leonard A. Kalman, M.D., Oncology Hematology Associates, Miami, Florida; Manuel R. Modiano, M.D., Arizona Clinical Research Center, Tucson, Arizona; Hemant K. Patel, M.D., Northwest Alabama Cancer Center, Muscle Shoals, Alabama; Myo Thant, M.D., Franklin Square Hospital Center, Baltimore, Maryland; Guy W. Amsden, Pharm. D., Clinical Drug Research Center, Worcester, Massachusetts; Kenneth C. Caldwell, M.D., St. Paul Hematology/Oncology, Inc., St. Paul, Minnesota; Sant P. Chawla, M.D., Santa Monica, California; John M. Feigert, M.D., Arlington Fairfax Hematology Oncology, Arlington, Virginia; John D. Hainsworth, M.D., Sarah Cannon Cancer Center, Nashville, Tennessee; Walter H. Harvey, D.O., Hematology/Oncology Associates of SW Florida, Naples, Florida; Michael McCleod, M.D., Island Coast Hematology and Oncology, Fort Myers, Florida; Robert M. Post, M.D., Hematology/Oncology Associates, Allentown, Pennsylvania; Joan H. Schiller, M.D., University of Wisconsin Hospital, Madison, Wisconsin; Stanley Winokur, M.D., Georgia Cancer Specialists, Atlanta, Georgia.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 Conclusion
 References
 

  1. Hesketh PJ, Kris MG, Grunberg SM et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1997;15:103-109.[Abstract/Free Full Text]
  2. Clavel M, Soukop M, Greenstreet YLA. Improved control of emesis and quality of life with ondansetron in breast cancer. Oncology 1993;50:180-185.[Medline]
  3. Lindley CM, Hirsch JD, O'Neill CV et al. Quality of life consequences of chemotherapy-induced emesis. Qual Life Res 1992;1:331-340.[Medline]
  4. Gregory RE, Ettinger DS. 5-HT3-Receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting: a comparison of their pharmacology and clinical efficacy. Drugs 1998;55:173-189.[Medline]
  5. Perez EA, Hesketh PJ, Gandara DR. Serotonin antagonists in the management of cisplatin-induced emesis. Semin Oncol 1991;16:73-80.
  6. Aapro MS. Review of experience with ondansetron and granisetron. Ann Oncol 1993;4(suppl 3):9-14.[Free Full Text]
  7. Hainsworth JD. Development of serotonin antagonists for the control of chemotherapy-induced emesis. Semin Surg Oncol 1993;9:279-284.[Medline]
  8. Cubeddu LX, Hoffman IS, Fuenmayor NT et al. Efficacy of ondansetron (GR38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. N Engl J Med 1990;322:810-816.[Abstract]
  9. Navari R, Gandara D, Hesketh S et al. Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. J Clin Oncol 1995;13:1242-1248.[Abstract]
  10. Roila F, Tonato M, Cognetti F. Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone. J Clin Oncol 1991;9:675-678.[Abstract]
  11. Chavallier B. Efficacy and safety of granisetron compared with high-dose metoclopramide plus dexamethasone in patients receiving high-dose cisplatin in a single blind-study. Eur J Cancer 1990;26(suppl 1):33-36.
  12. Addelman M, Erlichman C, Fine S et al. Phase I/II trial of granisetron: a novel 5-hydroxytryptamine antagonist for the prevention of chemotherapy-induced nausea and vomiting. J Clin Oncol 1990;8:337-341.[Abstract]
  13. Butcher ME. Global experience with ondansetron and future potential. Oncology 1993;50:191-197.[Medline]
  14. Bryson JC. Clinical safety of ondansetron. Semin Oncol 1992;19:26-32.
  15. Beck TM. Efficacy of ondansetron tablets in the management of chemotherapy-induced emesis: review of clinical trials. Semin Oncol 1992;19(suppl 15):20-25.
  16. Gralla RJ, Navari RM, Hesketh PJ et al. Single dose oral granisetron has equivalent antiemetic efficacy to intravenous ondansetron for highly emetogenic cisplatin-based therapy. J Clin Oncol 1998;16:1568-1573.[Abstract/Free Full Text]
  17. Perez EA, Hesketh P, Sandbach J et al. Comparison of single-dose oral granisetron and intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study. J Clin Oncol 1998;16:754-760.[Abstract]
  18. Beck TM, Hesketh PJ, Madajewicz S et al. Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dosed regimens in the prevention of cisplatin-induced nausea and vomiting. J Clin Oncol 1992;10:1969-1975.[Abstract]
  19. Carmicheal J, Bessel EM, Hutcheon AW et al. Comparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis. Br J Cancer 1994;70:1161-1164.[Medline]
  20. Smythe JF, Coleman RE, Nicholson M et al. Does dexamethasone enhance control of acute cisplatin induced emesis by ondansetron? Br Med J 1991;303:1423-1426.
  21. Hesketh PJ, Harvey WH, Harker WG et al. A randomized, double-blind comparison of intravenous ondansetron alone and in combination with intravenous dexamethasone in the prevention of high-dose cisplatin-induced emesis. J Clin Oncol 1994;12:596-600.[Abstract]
  22. Joss RA, Bacchi M, Buser K et al. Ondansetron plus dexamethasone is superior to ondansetron alone in the prevention of emesis in chemotherapy-naïve and previously treated patients. Ann Oncol 1994;5:253-258.[Abstract/Free Full Text]
  23. Gandara DR, Roila F, Warr D et al. Consensus proposal for 5-HT3 antagonists in the prevention of acute emesis related to highly emetogenic chemotherapy. Support Care Cancer 1998; 6:237-243.[Medline]
  24. Warr D. Standard treatment of chemotherapy-induced emesis. Support Care Cancer 1997;5:12-16.[Medline]
  25. Krazakowski M, Graham E, Goedhals L. A multicenter, double-blind comparison of IV and oral administration of ondansetron plus dexamethasone for acute cisplatin-induced emesis. Anticancer Drugs 1998;9:593-598.[Medline]
  26. Berard CM, Mahoney CD. Cost-reducing treatment algorithms for antineoplastic drug-induced nausea and vomiting. Am J Health Syst Pharm 1995;52:1879-1885.
  27. US Balanced Budget Act of 1997: Coverage of Oral Anti-Nausea Drugs Under Chemotherapeutic Regimen. Sect. 4557a.
accepted for publication November 16, 1998.





This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow eLetters: Submit a response to this article
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints/Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Spector, J. I.
Right arrow Articles by Creed, M. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Spector, J. I.
Right arrow Articles by Creed, M. R.

HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
THE ONCOLOGIST STEM CELLS CME ALPHAMED PRESS JOURNALS