In Asian countries, paclitaxel once per week is used as second-line treatment in advanced gastric cancer, including human epidermal growth factor receptor 2 (HER2) -positive tumors. The role of ...anti-HER2 agents, including lapatinib, in this setting and population is unclear.
TyTAN was a two-part, parallel-group, phase III study in Asian patients. An open-label, dose-optimization phase (n = 12) was followed by a randomized phase (n = 261), in which patients who were HER2 positive by fluorescence in situ hybridization (FISH) received lapatinib 1,500 mg once per day plus once-per-week paclitaxel 80 mg/m(2) or paclitaxel alone. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), time to progression (TTP), overall response rate (ORR), time to response, response duration, and safety. Analyses were based on immunohistochemistry (IHC) and gastrectomy status, prior trastuzumab therapy, and regional subpopulations.
Median OS was 11.0 months with lapatinib plus paclitaxel versus 8.9 months with paclitaxel alone (P = .1044), with no significant difference in median PFS (5.4 v 4.4 months) or TTP (5.5 v 4.4 months). ORR was higher with lapatinib plus paclitaxel versus paclitaxel alone (odds ratio, 3.85; P < .001). Better efficacy with lapatinib plus paclitaxel was demonstrated in IHC3+ compared with IHC0/1+ and 2+ patients and in Chinese compared with Japanese patients. A similar proportion of patients experienced adverse events with each treatment (lapatinib plus paclitaxel, 100% v paclitaxel alone, 98%).
Lapatinib plus paclitaxel demonstrated activity in the second-line treatment of patients with HER2 FISH-positive IHC3+ advanced gastric cancer but did not significantly improve OS in the intent-to-treat population.
Background
Extensive‐stage small cell lung cancer (ES‐SCLC) is deemed as a fatal malignancy with a poor prognosis. Although immunotherapy has gradually played an important role in the treatment of ...ES‐SCLC since 2018, ES‐SCLC treatment data and patient outcome before 2018, when chemotherapy served as a fundamental therapeutic strategy, is still meaningful as a summary of the situation regarding previous medical treatment and is a baseline for comparative data. In addition, the prognostic factors of ES‐SCLC have failed to reach a consensus until now. Therefore, this study aimed to evaluate survival and identify the prognostic factors in an ES‐SCLC population.
Methods
We retrospectively collected the detailed medical records of 358 patients with ES‐SCLC from January 1, 2011 to December 31, 2018 in a Chinese top‐level cancer hospital. The prognostic factors were evaluated by Cox univariate and multivariate analysis.
Results
The median overall survival (OS) of ES‐SCLC patients (N = 358) was 14.0 months, the one‐ and two‐year OS rates were 56.2% and 21.7%, respectively. Moreover, we identified two demographic characters (age ≥ 70, smoking index ≥ 400), one tumor burden factor (bone multimetastasis), two tumor biomarkers (cyfra211, CA125) and two laboratory indexes (decreased Na, PLR < 76) as independent prognostic factors for OS in this patient population. Progression‐free survival (PFS) data of 238 patients was obtained for further analysis, and the median PFS was 6.2 months, and six‐month and one‐year PFS rates were 51.7% and 14.3%, respectively. Elevated cyfra211, decreased Hb and Na were identified as independent prognostic factors for PFS.
Conclusions
This study provides real‐world evidence of the survival and prognosis of ES‐SCLC patients which will enable better evaluation and clinical decision‐making in the future.
This study provides real‐world evidence of survival and prognosis of untreated extensive stage small cell lung cancer (ES‐SCLC). We retrospectively collected the detailed medical records of 358 patients with ES‐SCLC from 2011 to 2018 in a Chinese top‐level cancer hospital. The median overall survival (OS) of all patients was 14.0 months, and the one‐ and two‐year OS rates were 56.2% and 21.7%, respectively. The median progression‐free survival (PFS) of 238 patients was 6.2 months, and the six‐month and one‐year PFS rates were 51.7% and 14.3%, respectively. Moreover, several independent prognostic factors for OS and PFS of ES‐SCLC were identified.
AIM：To evaluate effects of UDP-glucuronosyltransferase1A1（UGT1A1） and thymidylate synthetase（TS） gene polymorphisms on irinotecan in metastatic colorectal cancer（mCRC）.METHODS：Two irinotecan-and ...fluorouracil-based regimens,FOLFIRI and IFL,were selected as second-line therapy for 138 Chinese mCRC patients.Genomic DNA was extracted from peripheral blood samples before treatment.UGT1A1 and TS gene polymorphisms were determined by direct sequencing and restriction fragment length polymorphism,respectively.Gene polymorphisms of UGT1A1＊28,UGT1A1＊6 and promoter enhancer region of TS were analyzed.The relationship between genetic polymorphisms and clinical outcome,that is,response,toxicity and survival were assessed.Pharmacokinetic analyses were performed in a subgroup patients based on different UGT1A1 genotypes.Plasma concentration of irinotecan and its active metabolite SN-38 and inactive metabolite SN-38G were determined by high performance liquid chromatography.Differences in irinotecan and its metabolites between UGT1A1 gene variants were compared.RESULTS：One hundred and eight patients received the FOLFIRI regimen,29 the IFL regimen,and one irinotecan monotherapy.One hundred and thirty patients were eligible for toxicity and 111 for efficacy evaluation.One hundred and thirty-six patients were tested for UGT1A1＊28 and ＊6 genotypes and 125 for promoter enhancer region of TS.Patients showed a higher frequency of wild-type UGT1A1＊28（TA6/6） compared with a Caucasian population（69.9% vs 45.2%）.No significant difference was found between response rates and UGT1A1 genotype,although wild-type showed lower response rates compared with other variants（17.9% vs 24.2% for UGT1A1＊28,15.7% vs 26.8% for UGT1A1＊6）.When TS was considered,the subgroup with homozygous UGT1A1＊28（TA7/7） and non-3RG genotypes showed the highest response rate（33.3%）,while wild-type UGT1A1＊28（TA6/6） with non-3RG only had a 13.6% response rate,but no significant difference was found.Logistic regression showed treatment duration was closely linked to clinical response.In toxicity comparison,UGT1A1＊28 TA6/6 was associated with lower incidence of grade 2-4 diarrhea（27.8% vs 100%）,and significantly reduced the risk of grade 4 neutropenia compared with TA7/7（7.8% vs 37.5%）.Wild-type UGT1A1＊6（G/G） tended to have a lower incidence of grade 3/4 diarrhea vs homozygous mutant（A/A） genotype（13.0% vs 40.0%）.Taking UGT1A1 and TS genotypes together,lower incidence of grade 2-4 diarrhea was found in patients with non-3RG TS genotypes,when TA6/6 was compared with TA7/7（35.3% vs 100.0%）.No significant association with time to progression（TTP） and overall survival（OS） was observed with either UGT1A1 or TS gene polymorphisms,although slightly longer TTP and OS were found with UGT1A1＊28（TA6/6）.Irinotecan PK was investigated in 34 patients,which showed high area under concentration curve（AUC） of irinotecan and SN-38,but low AUC ratio（SN-38G /SN-38） in those patients with UGT1A1＊28 TA7/7.CONCLUSION：A distinct distribution pattern of UGT1A1 genotypes in Chinese patients might contribute to relatively low toxicity associated with irinotecan and 5-fluorouracil in mCRC patients.
Background
Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small‐molecule ...multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double‐blinded, placebo‐controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.
Methods
Famitinib or placebo was administered orally once daily. The primary endpoint was progression‐free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality‐of‐life (QoL), and safety.
Results
Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41–0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3–4 adverse events were hypertension (11.1%), hand‐foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657).
Conclusion
Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.
Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO‐Gastrointestinal Symposium
Gambogic acid is a pure active compound isolated from the traditional Chinese medicinal plant gamboge (Garcinia morella Desv.). Based on the preliminary results of a phase I study, this phase IIa ...study compared the efficacy and safety of different dosage schedules of gambogic acid in patients with advanced malignant tumors.
Patients with advanced or metastases cancer who had not received any effective routine conventional treatment or who had failed to respond to the existing conventional treatment were randomly assigned to receive either 45 mg/m(2) gambogic acid intravenously from Days 1 to 5 of a 2-week cycle (Group A), or 45 mg/m(2) every other day for a total of five times during a 2-week cycle (Group B). The primary endpoint was objective response rate (ORR).
Twenty-one patients assigned to Group A and 26 to Group B were included in the final analysis. The ORRs were 14.3% in Group A and 0% in Group B. It was not possible to analyze the significant difference because one of the values was zero. The disease control rates (DCRs) were 76.2% in Group A and 61.5% in Group B (P = 0.0456). The observed adverse reactions were mostly Grades I and II, and occurred in most patients after administration of the trial drug. There was no significant difference in the incidence of adverse reactions between the two arms.
The preliminary results of this phase IIa exploratory study suggest that gambogic acid has a favorable safety profile when administered at 45 mg/m(2). The DCR was greater in patients receiving gambogic acid on Days 1 - 5 of a 2-week cycle, but the incidence of adverse reactions was similar irrespective of the administration schedule.
AIM:To analyze the clinicopathologic characteristics and prognostic factors of rectal neuroendocrine tumors.METHODS:The records of 48 patients with rectal neuroendocrine tumors who were treated at ...the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,Beijing,from March 2004 to September 2009were retrospectively reviewed.The clinicopathological data were extracted and analyzed,and patients were followed-up by telephone or follow-up letter to determine their survival status.Follow-up data were available for all 48 patients.Uni-and multivariate Cox regression analyses were performed to determine the prognostic factors significantly associated with overall survival.RESULTS:The tumors occurred mostly in the middle and lower rectum,and the most prominent symptoms experienced by patients were hematochezia and diarrhea.The median distance between the tumors andthe anal edges was 5.0±2.257 cm,and the median diameter of the tumors was 0.8±1.413 cm.The major pathological type was a typical carcinoid tumor,which accounted for 93.8%(45/48)of patients.Tumor-nodemetastasis(TNM)stagesⅠ,Ⅱ,ⅢandⅣtumors accounted for 78.8%,3.9%,9.6%and 7.7%of patients,respectively.The main treatment method,in 72.9%(35/48)of patients,was transanal extended excision.The 1-,3-and 5-year survival rates of the whole group of patients were 100%,93.7%,and 91.3%,respectively.Univariate analysis showed that age(P=0.032),tumor diameter(P<0.001),histological type(P<0.001),TNM stage(P<0.001),and surgical approach(P=0.002)were all prognostic factors.On multivariate analysis,only the pathological type was shown to be an independent prognostic factor(HR=2.797,95%CI:1.676-4.668,P=0.004).CONCLUSION:In patients with rectal neuroendocrine tumors,TNM stage Ⅰ is the most common stage found,and lymph node or distant metastases are rarely seen.The pathological type of the tumor is an independent prognostic factor.
We report the first prospective study of sunitinib for metastatic renal cell carcinoma (mRCC) in China.
Chinese mRCC patients received first-line sunitinib 50 mg daily (4/2 regimen). Overall survival ...(OS), progression-free survival (PFS), objective response rate and safety were assessed. Potential efficacy biomarkers were explored in post hoc analyses.
Median PFS was 61.7 weeks; median OS was 133.4 weeks; objective response rate was 31.1%. Most frequent adverse events (AEs) were: hand-foot syndrome (63.8%), decreased white blood cell count (52.4%), fatigue (51.4%) and decreased platelet count (51.4%). AEs were identified that predicted longer PFS and OS.
Sunitinib showed efficacy and manageable AE profile in treatment-naive Chinese mRCC patients. Larger prospective studies are required to confirm identified AEs as predictors of efficacy.
Background： Colorectal adenocarcinoma rarely occurred in adolescent. Clinical feature and prognosis of this population are not clear until now. In addition, DNA mismatch repair （MMR） status may ...relate to the early disease occurrence. The present study aimed to perform a retrospective analysis of adolescent patients with colorectal cancer, including clinicopathological characteristics and prognosis. Methods： The medical records of 11,503 patients diagnosed as colorectal cancer in Cancer Hospital, Chinese Academy of Medical Sciences from January 1999 to December 2009 were retrospectively reviewed. Finally, 19 patients who were between 10 and 20 years old were selected as the study group. We summarized the clinicopathological characteristics, analyzed the association with prognosis and assessed the expression of MMR protein by immunohistochemical method. Results： The most common primary site was the right colon in 7 patients. Ten patients had Stage III colorectal cancer, 5 patients had Stage IV disease. Signet ring cell carcinoma was the most frequent pathological type （7/19）. Deficient MMR was identified in 2 patients. The 5-year survival rate and median survival time were 23.2% and 26 months. Distant metastasis was identified as an independent prognostic factor （P = 0.02）. Conclusions： Colorectal cancer in Chinese adolescents was very rare. The chinese adolecents with colorectal cancer were frequently diagnosed in the right colon, as Stage Ⅲ/Ⅳdisease with signet ring cell carcinoma. The prognosis was relatively poor.
Famitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor. The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum. The purpose ...of this study was to examine the efficacy and safety of famitinib for the treatment of metastatic renal cell carcinoma (mRCC).
The data of famitinib in treating patients with mRCC from the single-center phases I and II clinical trials were analyzed. Famitinib was administered orally at the dose of 13-30 mg once daily until tumor progression, occurrence of intolerable adverse reactions or withdrawal of the informed consent.
A total of 24 patients with mRCC were treated including 17 patients at a dose of 25 mg once daily, 4 patients at a dose of 27 mg and 1 patient each at a dose of 13 mg, 20 mg and 30 mg, respectively. Twelve (50.0%) patients achieved partial response (PR) and 9 patients achieved stable disease (SD). Progressive disease was found in 3 (12.5%) patients. The disease control rate was 87.5%. The median follow-up time was 17.6 months; the median progression free survival (PFS) was 10.7 (95% CI 7.0-14.4) months; and the estimated median overall survival (OS) time was 33.0 (95% CI 8.7-57.3) months. The adverse drug reactions mainly included hypertension (54.1%), hand-foot skin reactions (45.8%), diarrhea (33.3%), mucositis (29.2%), neutropenia (45.8%), thrombocytopenia (29.2%), hyperlipidemia (41.7%) and proteinuria (41.7%). The incidence rate of grades 3 and 4 adverse events was low, mainly including hypertension 12.5%, hand-foot skin reactions 4.2%, neutropenia 4.2%, thrombocytopenia 4.2%, hyperlipidemia 4.2% and proteinuria 12.5%.
Famitinib has significant anti-tumor activity in mRCC. The common adverse reactions are generally manageable.
To analyze the clinicopathologic factors related to recurrence and metastasis of stage II or III colon cancer after radical resection.
The clinical and pathological data of 628 patients with stage II ...or III colon cancer after radical resection from Jan. 2005 to Dec. 2008 in our hospital were retrospectively reviewed and analyzed.
The overall recurrence and metastasis rate was 28.5% (179/628). The 5-year disease-free survival (DFS) rate was 70.3% and 5-year overall survival (OS) rate was 78.5%. Univariate analysis showed that age, smoking intensity, depth of tumor invasion, lymph node metastasis, TNM stage, gross classification, histological differentiation, blood vessel tumor embolus, tumor gross pathology, multiple primary tumors, preoperative and postoperative serum concentration of CEA and CA19-9, and the regimen of adjuvant chemotherapy were correlated to recurrence and metastasis of colon cancer after radical resection. Multivariate analysis showed that regional lymph node metastasis, TNM stage, the regi
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