The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.
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References
1.
SodaM., ChoiY.L., EnomotoM.Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature.2007; 448(7153): 561–566.
2.
SetoT., KiuraK., NishioM.CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): A single-arm, open-label, phase 1–2 study. Lancet Oncol.2013; 14(7): 590–598.
3.
SakamotoH., TsukaguchiT., HiroshimaS.CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell.2011; 19: 679–690.
4.
ZouH.Y., FribouletL., KodackD.P.PF-06463922, an ALK/ROS1 inhibitor, overcomes resistance to first and second generation ALK inhibitors in preclinical models. Cancer Cell.2015; 28(1): 70–81.
5.
GadgeelS.M., GandhiL., RielyG.J.Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): Results from the dose-finding portion of a phase ½ study. Lancet Oncol.2014; 15(10): 1119–1128.
ShawA.T., GandhiL., GadgeelS.Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: A single-group, multicenter, phase 2 trial. Lancet Oncol.2016; 17(2): 234–242.
8.
OuS.H.I., AhnJ.S., De PetrisL.Alectinib in crizotinib-refractory ALK-rearranged non-small-cell lung cancer: A phase II global study. J Clin Oncol.2016; 34(7): 661–668.
9.
FribouletL., LiN., KatayamaR.The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov.2014; 4(12): 1–12.
MarsiljeT.H., PeiW., ChenB.Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl) phenyl)-N4-(2-(isopropylsulfonyl) phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem.2013; 56(14): 5675–5690.
12.
ShawA.T., KimD.W., MehraR.Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med2014; 370: 1189–1197.
13.
RichlyH., KimT.M., SchulerM.Ceritinib in patients with advanced anaplastic lymphoma kinase-rearranged anaplastic large-cell lymphoma. Blood.2015; 126(10): 1257–1258.
14.
TanD.A., ShawA.T., MehraR.Ceritinib in Asian versus Caucasian patients (Pts) with advanced anaplastic lymphoma kinase (ALK)-rearranged (ALK+) NSCLC: Subgroup analysis of the ASCEND-1 trial. Proc Am Soc Clin Oncol.2014. Abstract 8078. http://meetinglibrary.asco.org/content/129599-144. Accessed April 5, 2016.
15.
TanD.S., AraujoA., ZhangJ., SignorovitchJ.E.Comparative efficacy of ceritinib and crizotinib in previously treated crizotinib-naïve anaplastic lymphoma kinase-positive (ALK+) advanced or metastatic non-small cell lung cancer (NSCLC): An adjusted indirect comparison. Proc Am Soc Clin Oncol.2015. Abstract 8058. http://meetinglibrary.asco.org/content/143947-156. Accessed April 5, 2016.
16.
MokT., SpigelD., FelipE.ASCEND-2: A single-arm, open-label, multicenter phase II study of ceritinib in adult patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) previously treated with chemotherapy and crizotinib (CRZ). Proc Am Soc Clin Oncol.2014. Abstract 8059. http://meetinglibrary.asco.org/content/144861-156. Accessed April 5, 2016.
17.
FelipE., OrlovS., ParkK.ASCEND-3: A single-arm, open-label, multicenter phase II study of ceritinib in ALK-naïve adult patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol.2015. Abstract 8060. http://meetinglibrary.asco.org/content/145907-156. Accessed April 5, 2016.
18.
GeoergerB., SchulteJ., ZwaanC.M.Phase I study of ceritinib in pediatric patients (Pts) with malignancies harboring a genetic alteration in ALK (ALK+): Safety, pharmacokinetic (PK), and efficacy results. Proc Am Soc Clin Oncol.2015. Abstract 10005. http://meetinglibrary.asco.org/content/146923-156. Accessed April 5, 2016.
19.
KhanS.A., BaumanJ.E., BurtnessB.Ceritinib in anaplastic thyroid cancer (ATC) with ALK abnormalities. Proc Am Soc Clin Oncol.2015. Abstract TPS6085. http://meetinglibrary.asco.org/content/147069-156. Accessed April 5, 2016.
20.
KimD., MehraR., TanD.S.Ceritinib in advanced anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC): Results of the ASCEND-1 trial. Proc Am Soc Clin Oncol.2014. Abstract 8003. http://meetinglibrary.asco.org/content/128749-144. Accessed April 5, 2016.
21.
PalumboA., SonneveldP.Preclinical and clinical evaluation of elotuzumab, a SLAMF-7 targeted humanized monoclonal antibody in development for multiple myeloma. Expert Rev Hematol.2015; 8(4): 481–491.
22.
LonialS., VijR., HarousseauJ.L.Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol.2012; 30(16): 1953–1959.
23.
ZonderJ.A., MohrbacherA.F., SinghalS.A phase I, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood.2012; 120(3): 552–559.
24.
BerdejaJ., JagannathS., ZonderJ.Pharmacokinetics and safety of elotuzumab combined with lenalidomide and dexamethasone in patients with multiple myeloma and various levels of renal impairment: Results of a phase Ib study. Clin Lymphoma Myeloma Leuk.2016; 16(3): 129–138.
RichardsonP.G., JagannathS., MoreauP.Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: Final phase 2 results from the randomized, open-label, phase 1b-2 dose-escalation study. Lancet Oncol.2015; 2(12): e516–527.
27.
LonialS., DimopoulosM., PalumboA.Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med.2015; 373(7): 621–631.
28.
SouersA.J., LeversonJ.D., BoghaertE.R.ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med.2013; 19(2): 202–208.
29.
RobertsA.W., DavidsM.S., PagelJ.M.Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med.2016; 374(4): 311–322.
30.
SeymourJ.F., DavidsM.S., PagelJ.M.Bcl-2 inhibitor ABT-199 (GDC-0199) monotherapy shows anti-tumor activity including complete remissions in high-risk relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Proc Am Soc Hematol.2013. Abstract 872. http://www.bloodjournal.org/content/122/21/872. Accessed April 5, 2016.
31.
DavidsM.S., SeymourJ.F., GerecitanoJ F.The single-agent Bcl-2 inhibitor ABT-199 (GDC-0199) in patients with relapsed/refractory (R/R) non-hodgkin lymphoma (NHL): Responses observed in all mantle cell lymphoma (MCL) patients. Proc Am Soc Hematol.2013. Abstract 1789. http://www.bloodjournal.org/content/122/21/1789. Accessed April 5, 2016.
FischerK., FinkA.M., BishopH.Results of the safety run-in phase of CLL14 (BO25323): A prospective, open-label, multicenter randomized phase iii trial to compare the efficacy and safety of obinutuzumab and venetoclax (GDC-0199/ABT-199) with obinutuzumab and chlorambucil in patients with previously untreated CLL and coexisting medical conditions. Proc Am Soc Hematol.2015. Abstract 496. http://www.bloodjournal.org/content/126/23/496. Accessed April 5, 2016.
34.
SallesG.A., BoydT.E., MorschhauserF.Updated safety and preliminary efficacy data from a phase 1b study combining venetoclax (GDC-0199, ABT-199) with bendamustine/rituximab in patients with relapsed/refractory or previously untreated chronic lymphocytic leukemia. Proc Am Soc Hematol.2015. Abstract 829. http://www.bloodjournal.org/content/126/23/829. Accessed April 5, 2016.
35.
GerecitanoJ.F., RobertsA.W., SeymourJ.F.A phase 1 study of venetoclax (ABT-199/GDC-0199) monotherapy in patients with relapsed/refractory non-Hodgkin lymphoma. Proc Am Soc Hematol.2015. Abstract 254. http://www.bloodjournal.org/content/126/23/254. Accessed April 5, 2016.
36.
TouzeauC., Chanan-KhanA.A.A., RobertsA.W.Phase 1b interim results: Venetoclax (ABT-199/GDC-0199) in combination with bortezomib (BTZ) and dexamethasone (Dex) in relapsed/refractory (R/R) multiple myeloma (MM). Proc Am Soc Clin Oncol.2015. Abstract 8580. http://meetinglibrary.asco.org/content/147784-156. Accessed April 5, 2016.
37.
DiNardoC., PollyeaD., PratzK.A phase 1b study of venetoclax (ABT-199/GDC-0199) in combination with decitabine or azacitidine in treatment-naive patients with acute myelogenous leukemia who are ≥ to 65 years and not eligible for standard induction therapy. Proc Am Soc Hematol.2015. Abstract 327 http://www.bloodjournal.org/content/126/23/327. Accessed April 5, 2016.
38.
MoreauP., Chanan-KhanA., RobertsA.W.Safety and efficacy of venetoclax (ABT-199/GDC-0199) in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma: Phase 1b results. Proc Am Soc Hematol.2015. Abstract 3038. http://www.bloodjournal.org/content/126/23/3038. Accessed April 5, 2016.
39.
SeymourJ.F., DavidsM.S., PagelJ.M.Updated results of a phase I first-in-human study of the BCL-2 inhibitor ABT-199 (GDC-0199) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Proc Am Soc Clin Oncol.2013. Abstract 7018. http://meetinglibrary.asco.org/content/116822-132. Accessed April 5, 2016.
40.
DavidsM.S., SeymourJ.F., GrecitanoJ.F.Updated results of a phase I first-in-human study of the BCL-2 inhibitor ABT-199 (GDC-0199) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL). Proc Am Soc Clin Oncol.2013. Abstract 8520. http://meetinglibrary.asco.org/content/117720-132. Accessed April 5, 2016.
41.
SeymourJ.F., DavidsM.S., PagelJ.M.ABT-199 (GDC-0199) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL): High complete- response rate and durable disease control. Proc Am Soc Clin Oncol.2014. Abstract 7015. http://meetinglibrary.asco.org/content/134145-144. Accessed April 5, 2016.
42.
DavidsM.S., SeymourJ F., GerecitanoJ F.Phase I study of ABT-199 (GDC-0199) in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL): Responses observed in diffuse large B-cell (DLBCL) and follicular lymphoma (FL) at higher cohort doses. Proc Am Soc Clin Oncol.2014. Abstract 8522. http://meetinglibrary.asco.org/print/1738430. Accessed April 5, 2016.
43.
RobertsA.W., MaS., BranderD.M.Determination of recommended phase 2 dose of ABT-199 (GDC-0199) combined with rituximab (R) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Proc Am Soc Hematol2014, abstract 325. http://www.bloodjournal.org/content/124/21/325. Accessed April 5, 2016.
44.
De VosS., FlowersC., WangD.Interim results from a dose-escalation study of the BCL-2 inhibitor venetoclax (ABT-199/GDC-0199) plus bendamustine (B) and rituximab (R) in patients (pts) with relapsed/refractory (R/R) Non-Hodgkin's Lymphoma (NHL). Proc Am Soc Clin Oncol.2015. Abstract 8535. http://meetinglibrary.asco.org/content/149632-156. Accessed April 5, 2016.
45.
KumarS., VijR., KaufmanJ.L.Phase I interim safety and efficacy of venetoclax (ABT-199/GDC-0199) monotherapy for relapsed/refractory (R/R) multiple myeloma (MM). Proc Am Soc Clin Oncol.2015. Abstract 8576. http://meetinglibrary.asco.org/content/151052-156. Accessed April 5, 2016.
46.
StilgenbauerS., EichhorstB.F., ScheteligJ.Venetoclax (ABT-199/GDC-0199) monotherapy induces deep remissions, including complete remission and undetectable MRD, in ultrahigh risk relapsed/refractory chronic lymphocytic leukemia with 17p deletion: Results of the pivotal international phase 2 study. Proc Am Soc Hematol.2015. Abstract LBA-6. http://www.bloodjournal.org/content/126/23/LBA-6. Accessed April 5, 2016.
47.
de VosS., SwinnenL., KozloffM. A dose-escalation study of venetoclax (ABT-199/GDC-0199) in combination with bendamustine and rituximab in patients with relapsed or refractory non-Hodgkin's lymphoma. Proc Am Soc Hematol.2015. Abstract 255. http://www.bloodjournal.org/content/126/23/255. Accessed April 5, 2016.
48.
MaS., BranderD.M., SeymourJ.F.Deep and durable responses following venetoclax (ABT-199/GDC-0199) combined with rituximab in patients with relapsed/refractory chronic lymphocytic leukemia: Results from a phase 1b study. Proc Am Soc Hematol.2015. Abstract 830. http://www.bloodjournal.org/content/126/23/830. Accessed April 5, 2016.
49.
KumarS.K., VijR., KaufmanJ.L.Safety and efficacy of venetoclax (ABT-199/GDC-0199) monotherapy for relapsed/refractory multiple myeloma: Phase 1 preliminary results. Proc Am Soc Hematol.2015. Abstract 4219. http://www.bloodjournal.org/content/126/23/4219. Accessed April 5, 2016.
50.
JonesJ., MatoA.R., CoutreS.Preliminary results of a phase 2, open-label study of venetoclax (ABT-199/GDC-0199) monotherapy in patients with chronic lymphocytic leukemia relapsed after or refractory to ibrutinib or idelalisib therapy. Proc Am Soc Hematol.2015. Abstract 715. http://www.bloodjournal.org/content/126/23/715. Accessed April 5, 2016.
51.
MaS., SeymourJ.F., LanasaM.C.ABT-199 (GDC-0199) combined with rituximab (R) in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Interim results of a phase 1b study. Proc Am Soc Clin Oncol.2014. Abstract 7013. http://meetinglibrary.asco.org/content/132375-144. Accessed April 5, 2016.