Clinical Implications of the Pharmacokinetics of Crizotinib in Populations of Patients with Non–Small Cell Lung Cancer

Wang, Erjian; Nickens, Dana; Bello, Akintunde; Khosravan, Reza; Amantea, Michael; Wilner, Keith D.; Parivar, Kourosh; Tan, Weiwei

doi:10.1158/1078-0432.ccr-16-0536

Cited by 23 publications

(16 citation statements)

References 12 publications

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“…The efficacy of crizotinib is optimal at a dose of 250 mg twice daily. A recent study on crizotinib pharmacokinetics revealed that crizotinib at a starting dose appeared to be effective and tolerable, regardless of race, age, sex, hepatic function, or mild to moderate renal impairment (10). Since the hepatitis in the present case was not dose-dependent, the crizotinib dose was increased to the greater extent possible.…”

Section: Discussionmentioning

confidence: 59%

Successful oral desensitization with crizotinib after crizotinib‑induced hepatitis in an anaplastic lymphoma kinase‑rearranged non‑small‑cell lung cancer patient: A case report

et al. 2017

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Abstract. Crizotinib is one of the molecularly-targeted agents targeted against anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC). Although its effects appear to be promising, crizotinib may cause adverse effects in patients with ALK-rearranged NSCLC. Hepatic laboratory abnormalities are frequently observed with crizotinib and treatment discontinuation is occasionally required. We herein report the case of a 51-year-old woman diagnosed with relapsed ALK-rearranged NSCLC, who received crizotinib as second-line systemic chemotherapy. After 17 days of crizotinib therapy, the patient developed grade >3 hepatotoxicity. Treatment discontinuation improved the laboratory abnormalities and fifth-line oral desensitization with crizotinib achieved successful response without hepatotoxicity. Therefore, oral desensitization with crizotinib may be a viable option following crizotinib-induced hepatitis.

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Section: Discussionmentioning

confidence: 59%

Successful oral desensitization with crizotinib after crizotinib‑induced hepatitis in an anaplastic lymphoma kinase‑rearranged non‑small‑cell lung cancer patient: A case report

et al. 2017

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“…Furthermore, cigarette smoking induces cytochromes CYP1A1/1A2 and is hypothesized to alter anti-EGFR erlotinib pharmacokinetics, resulting in worse clinical outcomes [24, 25]. Crizotinib elimination via CYP1A1/1A2 has not been reported, yet our data suggests cigarette smoking has a potential impact on its pharmacokinetics [26, 27]. Nevertheless, only 29 patients were current smokers at time of crizotinib initiation in our study.…”

Section: Discussionmentioning

confidence: 85%

Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study

et al. 2017

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Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK-positive non-smallcell lung cancer (NSCLC) is not documented. We sought to assess OS with crizotinib in unselected ALK-positive NSCLC patients and whether post-progression systemic treatments affect survival outcomes.ALK-positive NSCLC patients receiving crizotinib in French expanded access programs or as approved drug were enrolled. We collected clinical and survival data, RECIST-defined progressive disease (PD) and post-PD systemic treatment efficacy. We performed multivariable analysis of OS from crizotinib initiation and PD under crizotinib. Unselected ALK-positive NSCLC patients achieve good survival outcomes with crizotinib therapy. Next-generation ALKi may provide survival improvement after PD under crizotinib.

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“…Various factors, including race, affect drug pharmacokinetics. Differences observed between Western and Asian patients in exposure to some drugs may be attributable to factors such as body weight and drug metabolism [13,14]. The recommended Phase II regimen of adavosertib for use in combination with paclitaxel and carboplatin in Western patients is 225 mg bid for 2.5 days [10].…”

Section: Discussionmentioning

confidence: 99%

Safety, Pharmacokinetics, and Clinical Activity of Adavosertib in Combination with Chemotherapy in Asian Patients with Advanced Solid Tumors: Phase Ib Study

Kato¹,

Souza

Kim

et al. 2020

Targ Oncol

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Background The WEE1 inhibitor adavosertib (AZD1775) has been investigated in Western patients.Objective This open-label Phase Ib study (NCT02341456) investigated the safety, pharmacokinetics, and clinical activity of adavosertib in combination with carboplatin alone or paclitaxel plus carboplatin in Asian patients with advanced solid tumors and defined the recommended Phase II dose. Patients and methods Nineteen patients received adavosertib 175 mg twice daily (bid) for 2.5 days (five doses) in combination with carboplatin (AUC 5) alone or paclitaxel (175 mg/m 2 ) plus carboplatin, or adavosertib 225 mg bid for 2.5 days in combination with paclitaxel plus carboplatin in 21-day cycles. Preliminary safety and dose-limiting toxicity analyses were performed and dose escalation/de-escalation conducted as appropriate. Results Adavosertib 175 mg bid for 2.5 days with carboplatin alone or paclitaxel plus carboplatin was considered tolerable. Two patients receiving adavosertib 225 mg bid in combination with paclitaxel plus carboplatin experienced dose-limiting toxicities (grade 4 sepsis; grade 5 acute respiratory distress syndrome); this regimen was not considered tolerable. Grade ≥ 3 adverse events reported most commonly in any cohort included: anemia; decreased white blood cell count; decreased neutrophil count; neutropenia; decreased platelet count; thrombocytopenia; and febrile neutropenia. Exposure to adavosertib, as determined by pharmacokinetic analysis, in Asian patients was higher than that previously seen in Western patients. A partial response occurred in 2/12 evaluable patients (16.7%) at the recommended Phase II dose. Conclusions Adavosertib 175 mg bid for 2.5 days was chosen as the recommended Phase II dose in combination with paclitaxel and carboplatin in Asian patients.

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Clinical Implications of the Pharmacokinetics of Crizotinib in Populations of Patients with Non–Small Cell Lung Cancer

Cited by 23 publications

References 12 publications

Successful oral desensitization with crizotinib after crizotinib‑induced hepatitis in an anaplastic lymphoma kinase‑rearranged non‑small‑cell lung cancer patient: A case report

Successful oral desensitization with crizotinib after crizotinib‑induced hepatitis in an anaplastic lymphoma kinase‑rearranged non‑small‑cell lung cancer patient: A case report

Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study

Safety, Pharmacokinetics, and Clinical Activity of Adavosertib in Combination with Chemotherapy in Asian Patients with Advanced Solid Tumors: Phase Ib Study

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