Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

The epidermal growth factor receptor (EGFR) signaling is aberrantly overexpressed in many solid malignancies, making it an important target for anti-cancer biologic agents. Among them, epidermal growth factor receptor inhibitors (EGFRIs), which have been widely used in clinical practice, include anti-EGFR monoclonal antibodies and tyrosine kinase inhibitors. A proportion of patients treated with EGFRIs develop specific, dose-dependent skin toxicity such as papulopustular rash, paronychia, xerosis and itch. These side effects can cause physical and psychosocial discomfort that may result in dose reduction, discontinuance, or replacement of the current EGFRIs treatment. Correct diagnosis and treatment of these skin and mucosal adverse effects associated with EGFRIs is of great significance for the tertiary prevention of malignant tumors. A review on EGFRI-related mucocutaneous adverse reactions is presented here, focusing on the pathogenesis, the various clinical manifestations, the strategies for prevention and treatment of these conditions.
Antibodies, Monoclonal/adverse effects* ; Antineoplastic Agents/therapeutic use* ; ErbB Receptors/therapeutic use* ; Humans ; Neoplasms/drug therapy* ; Protein Kinase Inhibitors/therapeutic use*

Osimertinib-induced interstitial lung disease (ILD) is an uncommon, but fatal pulmonary toxicity in some patients. We report a case of a 64-year-old male with stage IV adeno-non-small cell lung cancer (NSCLC) harboring an exon 19 deletion in the epidermal growth factor receptor (EGFR) treated with osimertinib 80 mg/d for first-line targeted therapy. On day 60 after initiating treatment of osimertinib, the patient developed ILD. Osimertinib was discontinued immediately and oral prednisone 60 mg/d was initiated, ILD improved within 13 d. After balancing the risk and benefit, osimertinib was restarted concurrently with prednisone. The patient showed neither disease progression nor a recurrence of ILD for more than 16 months. Based on our case and literature review, retreatment with osimertinib under steroid coverage could be considered as an effective treatment option after careful risk-benefit assessment for patients with EGFR-mutant NSCLC.
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Acrylamides/therapeutic use* ; Aniline Compounds/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Diseases, Interstitial/genetics* ; Lung Neoplasms/genetics* ; Male ; Middle Aged ; Prednisone ; Protein Kinase Inhibitors/adverse effects*

ErbB receptor tyrosine kinase inhibitors (EGFR-TKI), gefitinib, erlotinib, icotinib and aftinib, which are approved as a frontline treatment for patients with non-small cell lung cancer (NSCLC) who have tumors harboring EGFR mutations in China. And osimertinib was approved in second line setting for patients with EGFRT 790M-positive NSCLC. Rash, paronychia, diarrhea, stomatitis, liver dysfunction and (interstitial lung disease, ILD) are frequently observed in patients treated with EGFR-TKI. Chinese Society of Lung Cancer, Chinese Anti-Cancer Association, organized Chinese experts to develop the Chinese expert consensus on EGFR-TKI adverse event (AE) management based on domestic diagnosis and treatment of ADR and also incorporating international updated theory and recommendations.
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Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; genetics ; China ; Diarrhea ; etiology ; ErbB Receptors ; antagonists & inhibitors ; genetics ; metabolism ; Humans ; Liver Diseases ; etiology ; Lung Diseases ; etiology ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Stomatitis ; etiology

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies. Methods: ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout. Results: ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population. Conclusions: Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population. Clinical Trial Identifier NCT00856544 and NCT00413699.
Administration, Oral ; Adult ; Aged ; Arthritis, Rheumatoid ; drug therapy ; Asian Continental Ancestry Group ; Female ; Humans ; Male ; Middle Aged ; Piperidines ; adverse effects ; therapeutic use ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Pyrimidines ; adverse effects ; therapeutic use ; Pyrroles ; adverse effects ; therapeutic use ; Surveys and Questionnaires ; Young Adult

OBJECTIVEThis study aims to evaluate the efficacy and safety of crizotinib for advanced ALK-positive non-small cell lung cancer (NSCLC) patients.

METHODSTwenty-eight patients with advanced ALK-positive NSCLC were given orally crizotinib 250 mg b. i.d., and were followed up to evaluate the therapeutic efficacy and safety.

RESULTSAmong the 28 patients, the objective response rate (ORR) was 71.4% (20/28) and disease control rate (DCR) was 92.9% (26/28). Three patients achieved complete response. Seventeen patients had partial response. The most common drug-related adverse events were mild flickering vision and gastrointestinal reaction. Eleven patients experienced flickering vision. Nine patients had nausea and vomiting. Eight patients had diarrhea. They were all reversible and of grade I or II. Only one patient had grade III myelosuppression. Among the 28 patients, 16 cases were disease-free and 12 cases had progressive disease, with a progression-free survival of 8.2 months.

CONCLUSIONSCrizotinib is effective and tolerable in the treatment of advanced ALK-positive NSLCC. However, its long-term treatment efficacy requires to be further studied.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; pathology ; Nausea ; chemically induced ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Pyrazoles ; adverse effects ; therapeutic use ; Pyridines ; adverse effects ; therapeutic use ; Receptor Protein-Tyrosine Kinases ; Vomiting ; chemically induced

No abstract available.
Adult ; Antineoplastic Agents/*adverse effects ; Antitubercular Agents/therapeutic use ; Biopsy ; Female ; Gastrointestinal Stromal Tumors/*drug therapy/pathology/surgery ; Humans ; Imatinib Mesylate/*adverse effects ; Lung Diseases, Interstitial/*chemically induced/diagnosis ; Mycobacterium tuberculosis/*isolation & purification ; Protein Kinase Inhibitors/*adverse effects ; Rectal Neoplasms/*drug therapy/pathology/surgery ; Tomography, X-Ray Computed ; Tuberculosis, Pulmonary/diagnosis/drug therapy/*microbiology

OBJECTIVETo study the efficacy and safety of Chinese Childhood Leukemia Group ALL 2008 (CCLG-ALL2008) protocol combined with tyrosine kinase inhibitor (TKI, imatinib) for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in children.

METHODSThe clinical data of 53 patients aged less than 15 years when first diagnosed with Ph+ ALL between October 2008 and December 2013 were retrospectively analyzed. The patients were assigned to two groups: HR (n=26) and HR+TKI (n=27). The HR group was treated with CCLG-ALL2008 protocol (for high-risk patients). The HR+TKI group was treated with imatinib in combination with CCLG-ALL2008 protocol (for high-risk patients).

RESULTSThe complete remission rate and chemotherapy induction-related mortality rate in the TKI+HR and HR groups were 100% vs 75% and 0 vs 15%, respectively. The 3-year event-free survival (EFS) rate in the HR group was (6±5)%; the 5-year EFS rate of the TKI+HR group was (52±11)%. Compared with the HR group, the TKI+HR group had no increase in the toxic responses to chemotherapy and had a decrease in the infection rate during the induction period.

CONCLUSIONSApplication of imatinib significantly improves the clinical efficacy in children with Ph+ ALL and has good safety.

Adolescent ; Antineoplastic Agents ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Imatinib Mesylate ; adverse effects ; therapeutic use ; Male ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; mortality ; Protein Kinase Inhibitors ; therapeutic use

BACKGROUND/AIMS: The aim of this study was to assess the efficacy and safety of tofacitinib (5 and 10 mg twice daily) in patients with active rheumatoid arthritis (RA). METHODS: A systematic review of randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib in patients with active RA was performed using the Medline, Embase, and Cochrane Controlled Trials Register databases as well as manual searches. RESULTS: Five RCTs, including three phase-II and two phase-III trials involving 1,590 patients, met the inclusion criteria. The three phase-II RCTs included 452 patients with RA (144 patients randomized to 5 mg of tofacitinib twice daily, 156 patients randomized to 10 mg of tofacitinib twice daily, and 152 patients randomized to placebo) who were included in this meta-analysis. The American College of Rheumatology 20% response rate was significantly higher in the tofacitinib 5- and 10-mg groups than in the control group (relative risk [RR], 2.445; 95% confidence interval [CI], 1.229 to 4.861; p = 0.011; and RR, 2.597; 95% CI, 1.514 to 4.455; p = 0.001, respectively). The safety outcomes did not differ between the tofacitinib 5- and 10-mg groups and placebo groups with the exception of infection in the tofacitinib 10-mg group (RR, 2.133; 95% CI, 1.268 to 3.590; p = 0.004). The results of two phase-III trials (1,123 patients) confirmed the findings in the phase-II studies. CONCLUSIONS: Tofacitinib at dosages of 5 and 10 mg twice daily was found to be effective in patients with active RA that inadequately responded to methotrexate or disease-modifying antirheumatic drugs, and showed a manageable safety profile.
Antirheumatic Agents/administration & dosage/adverse effects/*therapeutic use ; Arthritis, Rheumatoid/*drug therapy ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Humans ; Janus Kinases/antagonists & inhibitors ; Methotrexate/therapeutic use ; Piperidines/administration & dosage/adverse effects/*therapeutic use ; Protein Kinase Inhibitors/administration & dosage/adverse effects/therapeutic use ; Pyrimidines/administration & dosage/adverse effects/*therapeutic use ; Pyrroles/administration & dosage/adverse effects/*therapeutic use ; Randomized Controlled Trials as Topic ; Treatment Outcome

Carcinoma, Non-Small-Cell Lung ; drug therapy ; Humans ; Lung Diseases, Interstitial ; chemically induced ; diagnosis ; Male ; Middle Aged ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Pyrazoles ; adverse effects ; therapeutic use ; Pyridines ; adverse effects ; therapeutic use