SPRYCEL (Page 7 of 9)
Advanced Phase CML and Ph+ ALL
Dose-Optimization Study: One randomized open-label study was conducted in patients with advanced phase CML (accelerated phase CML, myeloid blast phase CML, or lymphoid blast phase CML) to evaluate the efficacy and safety of SPRYCEL administered once daily compared with SPRYCEL administered twice daily. The primary efficacy endpoint was MaHR. A total of 611 patients were randomized to either the SPRYCEL 140 mg once daily or 70 mg twice daily group. Median duration of treatment was approximately 6 months for both treatment groups. The once daily schedule demonstrated comparable efficacy (non-inferiority) to the twice daily schedule on the primary efficacy endpoint.
The efficacy and safety of SPRYCEL were also investigated in patients with Ph+ ALL in one randomized study (starting dosage 140 mg once daily or 70 mg twice daily) and one single-arm study (starting dosage 70 mg twice daily). The primary efficacy endpoint was MaHR. A total of 130 patients were enrolled in these studies. The median duration of therapy was 3 months.
Response rates are presented in Table 8.
| 140 mg Once Daily | ||||
|---|---|---|---|---|
| Accelerated(n=158) | Myeloid Blast(n=75) | Lymphoid Blast(n=33) | Ph+ ALL(n=40) | |
| a Hematologic response criteria (all responses confirmed after 4 weeks): Major hematologic response: (MaHR) = complete hematologic response (CHR) + no evidence of leukemia (NEL). CHR: WBC ≤ institutional ULN, ANC ≥1000/mm3 , platelets ≥100,000/mm3 , no blasts or promyelocytes in peripheral blood, bone marrow blasts ≤5%, <5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood <20%, and no extramedullary involvement. NEL: same criteria as for CHR but ANC ≥500/mm3 and <1000/mm3 , or platelets ≥20,000/mm3 and ≤100,000/mm3. | ||||
| b MCyR combines both complete (0% Ph+ metaphases) and partial (>0%–35%) responses. | ||||
| CI = confidence interval ULN = upper limit of normal range. | ||||
| MaHR a | 66% | 28% | 42% | 38% |
| (95% CI) | (59–74) | (18–40) | (26–61) | (23–54) |
| CHRa | 47% | 17% | 21% | 33% |
| (95% CI) | (40–56) | (10–28) | (9–39) | (19–49) |
| NELa | 19% | 11% | 21% | 5% |
| (95% CI) | (13–26) | (5–20) | (9–39) | (1–17) |
| MCyR b | 39% | 28% | 52% | 70% |
| (95% CI) | (31–47) | (18–40) | (34–69) | (54–83) |
| CCyR | 32% | 17% | 39% | 50% |
| (95% CI) | (25–40) | (10–28) | (23–58) | (34–66) |
In the SPRYCEL 140 mg once daily group, the median time to MaHR was 1.9 months for patients with accelerated phase CML, 1.9 months for patients with myeloid blast phase CML, and 1.8 months for patients with lymphoid blast phase CML.
In patients with myeloid blast phase CML, the median duration of MaHR was 8 months and 9 months for the 140 mg once daily group and the 70 mg twice daily group, respectively. In patients with lymphoid blast phase CML, the median duration of MaHR was 5 months and 8 months for the 140 mg once daily group and the 70 mg twice daily group, respectively. In patients with Ph+ ALL who were treated with SPRYCEL 140 mg once daily, the median duration of MaHR was 4.6 months. The medians of progression-free survival for patients with Ph+ ALL treated with SPRYCEL 140 mg once daily and 70 mg twice daily were 4.0 months and 3.5 months, respectively.
15 REFERENCES
- NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004–165.
- OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999, http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html.
- American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. (2006) 63:1172–1193.
- Polovich M, White JM, Kelleher LO (eds). 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd ed). Pittsburgh, PA: Oncology Nursing Society.
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
SPRYCEL® (dasatinib) tablets are available as described in Table 9.
| NDC Number | Strength | Description | Tablets per Bottle |
| 54868-5759-0 | 70 mg | white to off-white, biconvex, round, film-coated tablet with “BMS” debossed on one side and “524” on the other side | 60 |
16.2 Storage
SPRYCEL® tablets should be stored at 20° to 25°C (68° to 77°F); excursions permitted between 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].
16.3 Handling and Disposal
Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published [see References (15)].
SPRYCEL (dasatinib) tablets consist of a core tablet (containing the active drug substance), surrounded by a film coating to prevent exposure of pharmacy and clinical personnel to the active drug substance. However, if tablets are inadvertently crushed or broken, pharmacy and clinical personnel should wear disposable chemotherapy gloves. Personnel who are pregnant should avoid exposure to crushed or broken tablets.
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