Alternative schedules or integration strategies to maximise treatment duration with sunitinib in patients with gastrointestinal stromal tumours

Saponara,Maristella; Lolli,Cristian; Nannini,Margherita; Di Scioscio,Valerio; Serra,Carla; Mandrioli,Anna; Pallotti,Maria  Caterina; Biasco,Guido; Pantaleo,Maria   Abbondanza

doi:10.3892/ol.2014.2348

Alternative schedules or integration strategies to maximise treatment duration with sunitinib in patients with gastrointestinal stromal tumours

Authors:
- Maristella Saponara
- Cristian Lolli
- Margherita Nannini
- Valerio Di Scioscio
- Carla Serra
- Anna Mandrioli
- Maria Caterina Pallotti
- Guido Biasco
- Maria Abbondanza Pantaleo
View Affiliations

Affiliations: Department of Specialized, Experimental and Diagnostic Medicine, S.Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy, Department of Radiology, S.Orsola‑Malpighi Hospital, University of Bologna, Bologna 40138, Italy, Department of Digestive Disease and Internal Medicine, S.Orsola‑Malpighi Hospital, University of Bologna, Bologna 40138, Italy
Published online on: July 11, 2014 https://doi.org/10.3892/ol.2014.2348
Pages: 1793-1799

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumour of the gastrointestinal tract. The advent of targeted kinase‑inhibitors has revolutionised treatment strategies and clinical outcomes for patients with advanced GIST. In the majority of countries, sunitinib is the only approved second‑line treatment option for advanced GIST patients, who are resistant or intolerant to imatinib. However, sunitinib is associated with various adverse events, which often result in a reduction of the dosage, and interruption or suspension of therapy. Effective therapy management is essential to obtain the maximum clinical benefit, and includes adequate side effect management as well as optimization of dosing and treatment duration. In the current study, examples of maximization of treatment with sunitinib are presented, describing three clinical cases in which therapy with sunitinib was continued via the adoption of alternative reduced schedules or an additional loco‑regional treatment, in order to manage toxicities or overcome progressive disease.

View Figures

View References

1	Miettinen M and Lasota J: Gastrointestinal stromal tumors - definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch. 438:1–12. 2001.
2	Hirota S, Isozaki K, Moriyama Y, et al: Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 279:577–580. 1998.
3	Heinrich MC, Corless CL, Duensing A, et al: PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 299:708–710. 2003.
4	Dematteo RP, Heinrich MC, El-Rifai WM and Demetri G: Clinical management of gastrointestinal stromal tumors: before and after STI-571. Hum Pathol. 33:466–477. 2002.
5	Edmonson JH, Marks RS, Buckner JC and Mahoney MR: Contrast of response to dacarbazine, mitomycin, doxorubicin, and cisplatin (DMAP) plus GM-CSF between patients with advanced malignant gastrointestinal stromal tumors and patients with other advanced leiomyosarcomas. Cancer Invest. 20:605–612. 2002.
6	Demetri GD, von Mehren M, Blanke CD, et al: Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 347:472–480. 2002.
7	DeMatteo RP, Lewis JJ, Leung D, et al: Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. 231:51–58. 2000.
8	Antonescu CR, Besmer P, Guo T, et al: Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res. 11:4182–4190. 2005.
9	Mendel DB, Laird AD, Xin X, et al: In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 9:327–337. 2003.
10	Demetri GD, van Oosterom AT, Garrett CR, et al: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumor after failure of imatinib: a randomised controlled trial. Lancet. 368:1329–1338. 2006.
11	Demetri GD, Huang X, Garrett CR, et al: Novel statistical analysis of long-term survival to account for crossover in a phase III trial of sunitinib (SU) vs. placebo (PL) in advanced GIST after imatinib (IM) failure. J Clin Oncol. 26:105242008.
12	George S, Blay JY, Casali PG, et al: Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure. Eur J Cancer. 45:1959–1968. 2009.
13	Reichardt P, Kang Y, Ruka W, et al: Detailed analysis of survival and safety with sunitinib (SU) in a worldwide treatment-use trial of patients with advanced GIST. J Clin Oncol. 26(Suppl 15): 105482008.
14	Houk BE, Bello CL, Poland B, et al: Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis. Cancer Chemother Pharmacol. 66:357–371. 2010.
15	Saponara M, Pantaleo MA, Nannini M and Biasco G: Chronic therapy in gastrointestinal stromal tumors (GISTs): the big gap between theory and practice. Target Oncol. 7:243–246. 2012.
16	Joensuu H, Trent JC and Reichardt P: Practical management of tyrosine kinase inhibitor-associated side effects in GIST. Cancer Treat Rev. 37:75–88. 2011.
17	Najjar YG, Elson P, Wood LS, et al: Association of a 2-weeks-on and 1-week-off schedule of sunitinib with decreased toxicity in metastatic renal cell carcinoma. J Clin Oncol. 31(Suppl 6): 4062013.
18	Atkinson BJ, Kalra S, Wang X, Tannir NM and Jonasch E: A single-center retrospective review of outcomes associated with sunitinib alternative schedule compared to traditional schedule. J Clin Oncol. 31(Suppl 6): 3812013.
19	Britten CD, Kabbinavar F, Hecht JR, et al: A phase I and pharmacokinetic study of sunitinib administered daily for 2 weeks, followed by a 1-week off period. Cancer Chemother Pharmacol. 61:515–524. 2008.
20	Reichardt P, Kang YK, Rutkowski P, et al: Continued sunitinib treatment after progressive disease (PD) in a worldwide treatment-use trial of patients (pts) with gastrointestinal stromal tumor (GIST). In: Poster presented at the 37th ESMO congress; Vienna, Austria. September 28–October 2, 2012; (abstr 1490P).
21	Demetri GD, Reichardt P, Kang YK, et al: GRID study investigators: Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 381:295–302. 2013.
22	National Cancer Institute. National Cancer Institute common terminology criteria for adverse events version 4.0. http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. Accessed June 14, 2010
23	Maleddu A, Pantaleo MA, Nannini M, et al: Mechanisms of secondary resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumours (Review). Oncol Rep. 21:1359–1366. 2009.
24	Italiano A, Cioffi A, Coco P, et al: Patterns of care, prognosis, and survival in patients with metastatic gastrointestinal stromal tumors (GIST) refractory to first-line imatinib and second-line sunitinib. Ann Surg Oncol. 19:1551–1559. 2012.
25	Kinirons MT and O’Mahony MS: Drug metabolism and ageing. Br J Clin Pharmacol. 57:540–544. 2004.
26	Antoun S, Baracos VE, Birdsell L, Escudier B and Sawyer MB: Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma. Ann Oncol. 21:1594–1598. 2010.
27	Telli ML, Witteles RM, Fisher GA and Srinivas S: Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Ann Oncol. 19:1613–1618. 2008.
28	Rini BI, Cohen DP, Lu DR, et al: Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst. 103:763–773. 2011.
29	George S, Reichardt P, Lechner T, et al: Hypertension as a potential biomarker of efficacy in patients with gastrointestinal stromal tumor treated with sunitinib. Ann Oncol. 23:3180–3187. 2012.
30	Schmidinger M, Vogl UM, Bojic M, et al: Hypothyroidism in patients with renal cell carcinoma: blessing or curse? Cancer. 117:534–544. 2011.
31	Puzanov I, Michaelson MD, Cohen DP, et al: Evaluation of hand-foot syndrome (HFS) as a potential biomarker of sunitinib (SU) efficacy in patients (pts) with metastatic renal cell carcinoma (mRCC) and gastrointestinal stromal tumor (GIST). J Clin Oncol. 29(Suppl): 211132011.
32	Eskens FA and Verweij J: The clinical toxicity profile of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors; a review. Eur J Cancer. 42:3127–3139. 2006.
33	DeMatteo RP, Maki RG, Singer S, et al: Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor. Ann Surg. 245:347–352. 2007.
34	Gronchi A, Fiore M, Miselli F, et al: Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg. 245:341–346. 2007.
35	Pantaleo MA, Di Battista M, Catena F, et al: Surgical debulking of gastrointestinal stromal tumors: is it a reasonable option after second-line treatment with sunitinib? J Cancer Res Clin Oncol. 134:625–630. 2008.
36	Hakimé A, Le Cesne A, Deschamps F, et al: A role for adjuvant RFA in managing hepatic metastases from gastrointestinal stromal tumors (GIST) after treatment with targeted systemic therapy using kinase inhibitors. Cardiovasc Intervent Radiol. 37:132–139. 2014.