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.
HonigbergLA, SmithAM, SirisawadM, The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci USA. 2010;107(29): 13075–13080.
2.
ChangBY, HuangMM, FrancescoM, The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells. Arthritis Res Ther. 2011;13(4):R115.
3.
HermanSE, GordonAL, HertleinE, Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011:117(23):6287–6296.
4.
PonaderS, ChenSS, BuggyJJ, The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood. 2012;119(5):1182–1189.
5.
AdvaniRH, BuggyJJ, SharmanJP, Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013;31(1):88–94.
6.
ChengS, MaJ, GuoA, BTK inhibition targets in vivo CLL proliferation through its effects on B-cell receptor signaling activity. Leukemia. 2014;28(3):649–657.
7.
DubovskyJA, BeckwithKA, NatarajanG, Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013;122(15):2539–2549.
8.
ByrdJC, FurmanRR, CoutreSE, Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32–42.
9.
SukbuntherngJ, JejurkarP, ChanS, Pharmacokinetics (PK) of ibrutinib in patients with chronic lymphocytic leukemia (CLL). Proc Am Soc Clin Oncol. 2013. Abstract 7056. http://meetinglibrary.asco.org/content/112607-132. Accessed May 14, 2014.
BurgerJA, GhiaP, PolliackA, Randomized, multicenter, open-label, phase III study of the BTK inhibitor ibrutinib versus chlorambucil in patients 65 years or older with treatment-naive CLL/SLL (RESONATE-2, PCYC-1115-CA). Proc Am Soc Clin Oncol. 2013. Abstract TPS7130. http://meetinglibrary.asco.org/content/114419-132. Accessed May 14, 2014.
15.
ByrdJC, BrownJR, O'BrienS, Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia [published online ahead of print 2014]. New Engl J Med. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1400376. Accessed June 5, 2014.
O'BrienS, FurmanRR, CoutreSE, Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: An open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014;15(1):48–58.
20.
LouryD, SukbuntherngJ, ClowF, Open label evaluation of ECG in patients with chronic lymphocytic leukemia (CLL) receiving ibrutinib monotherapy. Proc Am Soc Clin Oncol. 2013. Abstract 7057. http://meetinglibrary.asco.org/content/112638-132. Accessed May 14, 2014.
21.
WangML, RuleS, MartinP, Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369(6):507–516.
WangM, GordonLI, RuleS, A phase III study of ibrutinib in combination with bendamustine and rituximab (BR) in elderly patients with newly diagnosed mantle cell lymphoma (MCL). Proc Am Soc Clin Oncol. 2013. Abstract TPS8613. http://meetinglibrary.asco.org/content/113203-132. Accessed May 14, 2014.
25.
SallesGA, GopalAK, MartinP, An open-label phase II study of ibrutinib in patients with refractory follicular lymphoma. Proc Am Soc Clin Oncol. 2013. Abstract TPS8614. http://meetinglibrary.asco.org/content/113208-132. Accessed May 14, 2014.
PrewettM, HuberJ, LiY, Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res. 1999;59(20):5209–5218.
28.
BrunsCJ, LiuW, DavisDW, Vascular endothelial growth factor is an in vivo survival factor for tumor endothelium in a murine model of colorectal carcinoma liver metastases. Cancer. 2000;89(3):488–499.
29.
SweeneyP, KarashimaT, KimSJ, Anti-vascular endothelial growth factor receptor 2 antibody reduces tumorigenicity and metastasis in orthotopic prostate cancer xenografts via induction of endothelial cell apoptosis and reduction of endothelial cell matrix metalloproteinase type 9 production. Clin Cancer Res. 2002;8(8):2714–2724.
30.
SpratlinJL, CohenRB, EadensM, Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol. 2010;28(5):780–787.
HussainM, RathkopfDE, LiuG, A phase II randomized study of cixutumumab (IMC-A12: CIX) or ramucirumab (IMC‑1121B: RAM) plus mitoxantrone (M) and prednisone (P) in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) following disease progression (PD) on docetaxel (DCT) therapy. Proc Am Soc Clin Oncol Genitourinary Cancers Symposium. 2012. Abstract 97. http://meetinglibrary.asco.org/content/89033-116. Accessed May 15, 2014.
33.
FuchsCS, TomasekJ, YongCJ, Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): An international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31–39.
34.
ZhuAX, FinnRS, MulcahyMF, A phase II study of ramucirumab as first-line monotherapy in patients (pts) with advanced hepatocellular carcinoma (HCC). Proc Am Soc Clin Oncol. 2010. Abstract 4083. http://meetinglibrary.asco.org/content/50568-74. Accessed May 15, 2014.
35.
GarciaJA, HudesGR, ChoueiriTK, . Phase II study of IMC-1121B in patients with metastatic renal cancer (mRCC) following VEGFR-2 tyrosine kinase inhibitor (TKI) therapy (IMCL CP12-0605/NCT00515697). Proc Am Soc Clin Oncol Genitourinary Cancers Symposium. 2010. Abstract 326. http://meetinglibrary.asco.org/content/30312-73. Accessed May 19, 2014.
36.
WilkeH, CunninghamD, OhtsuA, A randomized, multicenter, double-blind, placebo (PBO)-controlled phase III study of paclitaxel (PTX) with or without ramucirumab (IMC-1121B; RAM) in patients (pts) with metastatic gastric adenocarcinoma, refractory to or progressive after first-line therapy with platinum (PLT) and fluoropyrimidine (FP). Proc Am Soc Clin Oncol. 2012. Abstract TPS4139. http://meetinglibrary.asco.org/content/93982-114. Accessed May 15, 2014.
37.
GrotheyA, TaberneroJ, RougierP, A randomized, double-blind, phase (Ph) III study of the irinotecan-based chemotherapy FOLFIRI plus ramucirumab (RAM) or placebo (PL) in patients (pts) with metastatic colorectal carcinoma (mCRC) progressive during or following first-line therapy with bevacizumab (BEV), oxaliplatin (OXALI), and a fluoropyrimidine (FP) (RAISE) (NCT01183780). Proc Am Soc Clin Oncol. 2012. Abstract TPS3634. http://meetinglibrary.asco.org/content/92144-114. Accessed May 15, 2014.
38.
ZhuAX, ChauI, BlancJF, A multicenter, randomized, double-blind, phase III study of ramucirumab (IMC-1121B; RAM) and best supportive care (BSC) versus placebo (PBO) and BSC as second-line treatment in patients (pts) with hepatocellular carcinoma (HCC) following first-line therapy with sorafenib (SOR). Proc Am Soc Clin Oncol. 2012. Abstract TPS4146. http://meetinglibrary.asco.org/content/92970-114. Accessed May 15, 2014.
39.
PensonRT, MooreKN, FlemingGF, A phase II, open-label, multicenter study of IMC-1121B (ramucirumab; RAM) monotherapy in the treatment of persistent or recurrent epithelial ovarian (EOC), fallopian tube (FTC), or primary peritoneal (PPC) carcinoma (CP12-0711/NCT00721162). Proc Am Soc Clin Oncol.2012. Abstract 5012. http://meetinglibrary.asco.org/content/92977-114. Accessed May 15, 2014.
40.
Garcia-CarboneroR, RiveraF, MaurelJ, A phase II, open-label study evaluating the safety and efficacy of ramucirumab combined with mFOLFOX-6 as first-line therapy in patients (pts) with metastatic colorectal cancer (mCRC): CP12-0709/NCT00862784. Proc Am Soc Clin Oncol Gastrointestinal Cancers Symposium. 2012. Abstract 533. http://meetinglibrary.asco.org/content/87794-115. Accessed May 15, 2014.
41.
YoshinoT, YamazakiK, YoshidaM, A phase (Ph) Ib study of irinotecan (IRI), levofolinate (LV), and 5-fluorouracil (5-FU) (FOLFIRI) plus ramucirumab (RAM; IMC-1121B) drug product in Japanese (JP) patients (pts) with metastatic colorectal carcinoma (mCRC) progressive during or following first-line therapy with bevacizumab (BEV), oxaliplatin (OXALI), and a fluoropyrimidine (FP) (CP12-1029/NCT01286818). Proc Am Soc Clin Oncol Gastrointestinal Cancers Symposium. 2013. Abstract 591. http://meetinglibrary.asco.org/content/106149-133. Accessed May 15, 2014.
42.
FuchsCS, TomasekJ, ChoJY, REGARD: A phase III, randomized, double-blinded trial of ramucirumab and best supportive care (BSC) versus placebo and BSC in the treatment of metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing combination therapy. Proc Am Soc Clin Oncol Gastrointestinal Cancers Symposium. 2013. Abstract LBA5. http://meetinglibrary.asco.org/content/106221-133. Accessed May 15, 2014.
43.
WilkeH, Van CutsemE, OhSC, RAINBOW: A global, phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastroesophageal junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy rainbow IMCL CP12-0922 (I4T-IE-JVBE). Proc Am Soc Clin Oncol Gastrointestinal Cancers Symposium. 2014. Abstract LBA7. http://meetinglibrary.asco.org/content/123363-143. Accessed May 15, 2014.
44.
MackeyJ, GelmonK, MartinM, TRIO-012: A multicenter, multinational, randomized, double-blind phase III study of IMC-1121B plus docetaxel versus placebo plus docetaxel in previously untreated patients with HER2-negative, unresectable, locally recurrent or metastatic breast cancer. Clin Breast Cancer. 2009;9(4):258–261.
45.
GaronEB, CaoD, AlexandrisE, A randomized, double-blind, phase III study of docetaxel and ramucirumab versus docetaxel and placebo in the treatment of stage IV non-small-cell lung cancer after disease progression after 1 previous platinum-based therapy (REVEL): Treatment rationale and study design. Clin Lung Cancer. 2012;13(6):505–509.
46.
CamidgeDR, BallasMS, DubeyS, A phase II, open-label study of ramucirumab (IMC-1121B), an IgG1 fully human monoclonal antibody (MAb) targeting VEGFR-2, in combination with paclitaxel and carboplatin as first-line therapy in patients (pts) with stage IIIb/IV non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol. 2010. Abstract 7588. http://meetinglibrary.asco.org/content/50989-74. Accessed May 15, 2014.
47.
CarvajalRD, WongMK, ThompsonJA, A phase II randomized study of ramucirumab (IMC-1121B) with or without dacarbazine (DTIC) in patients (pts) with metastatic melanoma (MM). Proc Am Soc Clin Oncol. 2010. Abstract 8519. http://meetinglibrary.asco.org/content/50441-74. Accessed May 15, 2014.
48.
VahdatLT, MillerK, SparanoJA, Randomized phase II study of capecitabine with or without ramucirumab (IMC-1121B) or IMC-18F1 in patients with unresectable, locally advanced or metastatic breast cancer (mBC) previously treated with anthracycline and taxane therapy (CP20-0903/NCT01234402). Proc Am Soc Clin Oncol. 2011. Abstract TPS151. http://meetinglibrary.asco.org/content/82467-102. Accessed May 15, 2014.
49.
PetrylakDP, ChiKN, VogelzangNJ, Randomized phase II study of docetaxel with or without ramucirumab (IMC-1121B) or icrucumab (IMC-18F1) in patients with urothelial transitional cell carcinoma (TCC) following progression on first-line platinum-based therapy. Proc Am Soc Clin Oncol. 2012. Abstract TPS4675. http://meetinglibrary.asco.org/content/95198-114. Accessed May 15, 2014.
50.
YardleyDA, OsborneCRC, RichardsPD, Interim safety results of eribulin (E) combined with ramucirumab (RAM) in patients (pts) with advanced metastatic breast cancer (MBC). Proc Am Soc Clin Oncol Breast Cancer Symposium. 2012. Abstract 110. http://meetinglibrary.asco.org/content/102543-125. Accessed May 15, 2014.
