Effective Crizotinib schedule for an elderly patient with ALK rearranged non-small-cell lung cancer: a case report

Abstract

BackgroundNon-small-cell lung cancers (NSCLCs) harboring translocations in anaplastic lymphoma kinase (ALK) are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib.Case presentationWe describe a case of post-operative local recurrence of lung adenocarcinoma in an 81 year-old male. He underwent radiation and received chemotherapy with docetaxel, but neither treatment regimen was effective. Following identification of ALK rearrangements, crizotinib treatment was initiated. After treatment with crizotinib for 5 days, adverse events including acute renal failure (grade 2/CTCAE ver4.0) and congestive heart failure (grade 3) occurred. Crizotinib modified treatment was required. Half dose of crizotinib treatment could not control tumor progression. Ultimately, crizotinib was administrated at a dose of 250 mg twice daily every 3 day dosing for 13 months with maintenance of the anti-tumor effect.ConclusionThis is the first case report that skip schedule was more effective than dose reduction daily in crizotinib administration for ALK rearranged NSCLC patient with severe adverse events.

A systematic review of non-standard dosing of oral anticancer therapies

“…Near CR on intermittent schedule. High WCC, fatigue, anaemia Nil Fukuizumi et al (2015) Japan [ 46 ] To describe management of crizotinib with dose reductions in 1 case Case report, sample = 1, indication: ALK positive NSCLC Dose variation: 250 mg bd, 250 mg od, 250 mg every 3 days, and 250 mg bd every 3 days, with dose interruptions. Licensed monotherapy starting dose:250 mg bd Significant tumor response on escalating to 250 mg bd.…”

“…Eight case studies reported a variety of alternative dosing strategies (Table 5 ). These small studies described non-standard dosing practices in patients receiving either imatinib for leukaemia or gastrointestinal stromal tumour (GIST) [ 41 , 44 , 48 ], crizotinib or eroltinib for NSCLC [ 42 , 46 , 47 ], vemurafenib for malignant melanoma [ 45 ], and sunitinib for RCC [ 43 ]. Some of the evaluated strategies included combinations of intermittent dosing, and various dose reductions in response to experienced toxicities.…”

“…For example, Faber and colleagues (2006) used imatinib in CML at doses ranging from to 300 mg to 600 mg, and frequencies ranging from one to five times a week in 12 patients, rather than a daily dose. This was considered a plausible treatment option for patients with persistent myelotoxicity [ 41 ] Other authors additionally suggested that non-standard dosing strategies may help to individualise treatment to reduce toxicities [ 46 , 47 ], maintain QoL and support patient compliance [ 43 ].…”

Acute Tubular Injury and Renal Arterial Myocyte Vacuolization Following Crizotinib Administration

“…Crizotinib was then administrated at a dose of 250 mg twice daily only every 3 day for 13 months with maintenance of the anti-tumor effect, but no information was available on renal function. [9] There is no clear physiopathological explanation for crizotinib influence on renal function. We believe mesenchymal epithelial transition growth factor (c-Met) expression in the normal adult nephron could partially explain this toxicity.…”

Crizotinib-induced Rectal Perforation with Abscess

“…Our patient was elderly and his body surface area was smaller than that of the average Japanese man, suggesting that his dose of crizotinib (on a dose to body weight basis) might have led to higher trough and peak levels. Fukuizumi et al ( 9 ) reported a successfully treated case in which a modification of the drug schedule was more effective than dose reduction for avoiding severe adverse events. Given the difficulties associated with crizotinib in our case, determining the dosage based on the body surface area (BSA)-rather than body weight-might have been better for avoiding gastrointestinal adverse events.…”