A Phase III Randomized Trial of Two Different Dosing by m8nf93ke000


									S E L E C T E D           A B S T R A C T S                       F R O M              A S C O              2 0 0 5

Abstract 8031   A Phase III Randomized Trial of Two Different
                Dosing Schedules of Erythropoietin in Patients
                With Cancer-Associated Anemia: North Central
                Cancer Treatment Group (NCCTG) Study N02C2
                D.P. Steensma, R. Molina, J.A. Sloan, D.A. Nikcevich, P.L. Schaefer, K.M. Rowland, Jr.,
                T. Dentchev, P.J. Novotny, L.K. Tschetter, S.R. Alberts, T.F. Hogan, A. Law, and
                C.L. Loprinzi; North Central Cancer Treatment Group
                Mayo Clinic, Rochester, MN; Iowa Oncology Research Association CCOP, Des Moines, IA; Duluth CCOP,
                Duluth, MN; Toledo Community Hospital Oncology Program CCOP, Toledo, OH; Carle Cancer Center
                CCOP, Urbana, IL; Altru Health System, Grand Forks, ND; Sioux Community Cancer Consortium, Sioux
                Falls, SD; Scottsdale CCOP, Scottsdale, AZ; and Geisinger Clinic and Medical Center CCOP, Danville, PA

                       ACKGROUND:   Weekly epoetin alfa therapy benefits anemic cancer patients, but less
                       frequent dosing of the drug would offer patients greater convenience. METHODS: At
                       16 NCCTG sites, 365 adults with nonmyeloid cancer-associated anemia (hemoglo-
                bin [Hgb] level < 12 g/dL for males, < 11 g/dL for females) received 3 doses of 40,000
                U of epoetin alfa subcutaneously (SC) on a weekly basis; based on degree of anemia, age,
                chemotherapy use, and type of tumor, 183 patients were randomized to continue standard
                weekly epoetin alfa and 182 were given 120,000 U of epoetin alfa SC every 3 weeks for 18
                additional weeks. All patients received 324 mg of ferrous sulfate orally once daily. Eligible
                patients had an ECOG performance status of 0–2 and did not have iron deficiency or
                need active antineoplastic therapy (although 89% were receiving cancer therapy). The
                primary endpoint was the red blood cell (RBC) transfusion requirement of each group;
                secondary endpoints included changes in Hgb levels and quality of life (QOL) scores
                from baseline and toxicity. Between treatment groups, there was 80% power to detect a
                9% difference in the need for transfusion and an 8% difference in QOL score. RESULTS:
                No difference in the overall transfusion rate (23% in 40,000-U arm, 18% in 120,000-U
                arm; P = 0.22) was noted. Patients given the 40,000-U dose were more likely to have a
                ≥ 2- or ≥ 3-g/dL Hgb level increase from baseline (77% vs 67% for 2 g/dL; P = 0.05);
                these patients also had a slightly higher final Hgb level (12.0 vs 11.5; P = 0.0006) and a
                higher likelihood of exceeding an Hgb level >13 g/dL at some point (65% vs 43%; P <
                0.0001). Patients in the 40,000-U arm reported leukopenia more often (17% vs 10%; P =
                0.03) but did not have a higher infection rate. Other toxicities were equivalent. A slight
                trend toward superior survival was noted in the 120,000-U arm (P = 0.24). Patients on
                40,000 U of the drug had a higher global QOL using the Linear Analogue Self-Assess-
                ment measure at baseline (mean, 67 vs 62; P = 0.03) but a lesser improvement in QOL
                during the study (mean change, –0.3 vs +5.9; P = 0.02); thus, the end-of-study QOL was
                equivalent between arms. No differences in other QOL scores were noted. CONCLUSION:
                After 3 weekly doses, epoetin alfa may be given every 3 weeks at an equivalent total dose
                without increasing the need for transfusion or sacrificing QOL.

12              www.SupportiveOncology.net                                        THE JOURNAL OF SUPPORTIVE ONCOLOGY
                                                        A N E M I A

Q&A                                                                                                             Steensma et al
What are the possible cost implications for adapting the administration of epoetin alfa to
120,000 U every 3 weeks?
    The drug-specific costs for epoetin alfa given at a dose of 120,000 U every 3 weeks should be similar
to those incurred with the commonly used dosing schedule of 40,000 U weekly, since the total amount of
compound used is the same. However, there may be a cost savings for patients in terms of drug admin-
istration fees with every-3-week dosing, at least for those individuals who are unable to self-administer
epoetin alfa and need to receive it in their oncologists’ office. We are quite interested in exploring whether
doses of epoetin alfa lower than 120,000 U can be given every 3 weeks with similar effects to the120,000
U used in this study, perhaps resulting in even greater cost savings. It is possible that a lower dose of
epoetin alfa would saturate the recruitable erythropoietin receptors and would deliver identical results.
This should be studied in future clinical trials.
Would the results of this study convince you to administer epoetin alfa at 120,000 U every 3
weeks rather than 40,000 U weekly?
   I think this study demonstrates that doing so is a reasonable option. I have some patients in my practice
who commute from a considerable distance to get to the healthcare center and the ability to give these folks
epoetin alfa once every 3 weeks is useful. I know from talking with colleagues in rural states that visits to
the clinic can be a major issue in some areas—a patient in the Dakotas, for instance, who is living on the
sugar beet farm he grew up on and is now paying the unfortunate carcinomatous price for that Lucky Strikes
habit he picked up in World War II, may need every-3-week carboplatin and paclitaxel, and the nearest
oncologist is 80 miles away. That’s an awfully long drive just to get a weekly epoetin alfa shot when you’d
rather be helping with the harvest. The hemoglobin endpoints are not identical using epoetin alfa in this
way, but they are pretty close, and the ability to spare patients from transfusions appears to be the same.
                                                                                — David P Steensma, MD

                             P E E R          V I E W P O I N T

     C     omparisons of weekly versus every-3-week treatment programs are impor-
           tant in determining how best to use erythropoietic agents. In this NCCTG
     study, Steensma et al reported on a trial using epoetin alfa, dosed at either 40,000
     U weekly or 120,000 U every 3 weeks. This study also was designed to compare
     rates of RBC transfusion and found equal rates (23% weekly vs 32% every 3 weeks)
     with either regimen. Quality of life was similar for the two regimens.

     Along with the study by Canon et al (Abstract 8284; page 14), the results of these
     trials for patients with all types of solid tumors receiving nonspecific chemother-
     apy broadly suggested that either epoetin alfa or darbepoetin alfa given either
     every week or every 3 weeks is a useful supportive measure for cancer patients,
     with approximately similar levels of Hgb response, transfusion rate, and QOL. In
     principle, this flexibility affords clinicians the opportunity to choose their preferred
     agent and to link the treatment schedule to that most convenient and appropriate
     for the patient’s chemotherapy schedule.
                                                                   — Harold J. Burstein, MD, PhD

VOLUME 3, NUMBER 5, SUPPLEMENT 2      ■   SEPTEMBER/OCTOBER 2005             www.SupportiveOncology.net                    13

To top