Haiyi Guo

Fudan University, Shanghai, Shanghai Shi, China

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Publications (8)17.9 Total impact

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    ABSTRACT: The treatment choice of advanced gastric carcinoma after failure from first-line therapy is quite limited. To evaluate the efficacy and toxicity of S-1 monotherapy in patients with advanced gastric cancer after failure of first line cisplatin and fluorouracil combination (CF). S-1 monotherapy as a second line treatment was given to the patients who had failed to CF combination in SC-101 study. The efficacy and toxicity of S-1 monotherapy were evaluated exploratory. The results indicated that forty-one patients received S-1 as a second line therapy after disease progression. The overall response rate and disease control rate were 14.6% and 41.5%, respectively. The median progression free survival (PFS) was 5.1 months (range: 2.9~6.2 month). The median overall survival time was 6.4 months. The survival rates at 6 month and 1 year were 56% and 7.3%, respectively. Grade 3/4 adverse events were uncommonly occurred, including anemia (2.4%), neutropenia (2.4%), thrombocytopenia (4.9%) and rash (2.4%). There were no unexpected or life-threatening toxicities. Only one patient experienced dose reduction due to grade 3 rash. In conclusion, S-1 monotherapy provided a mild response rate and overall survival, and a favorable toxicity profile in the second line setting after the first line failure to cisplatin and fluorouracil combination.
    International journal of clinical and experimental pathology. 01/2014; 7(6):3293-8.
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    ABSTRACT: Human epidermal growth factor receptor 2 (HER2) is the most crucial ErbB receptor tyrosine kinase (RTK) family member in HER2-positive (refered to HER2-overexpressing) breast cancer which are dependent on or "addictive" to the Phosphatidylinositol-3-kinase (PI3K) pathway. HER2-related target drugs trastuzumab and lapatinib have been the foundation of treatment of HER2--positive breast cancer. This study was designed to explore the relationship between PI3K pathway activation and the sensitivity to lapatinib in HER2--positive metastatic breast cancer patients pretreated with anthracyclins, taxanes and trastuzumab. Sixty-seven HER2-positive metastatic breast cancer patients were recruited into a global lapatinib Expanded Access Program and 57 patients have primary tumor specimens available for determination of PI3K pathway status. PTEN status was determined by immunohistochemical staining and PIK3CA mutations were detected via PCR sequencing. All patients were treated with lapatinib 1250 mg/day continuously and capecitabine 1000 mg/m2 twice daily on a 2-week-on and 1-week-off schedule until disease progression, death, withdrawal of informed consent, or intolerable toxicity. PIK3CA mutations and PTEN loss were detected in 12.3% (7/57) and 31.6% (18/57) of the patients, respectively. Twenty-two patients with PI3K pathway activation (defined as PIK3CA mutation and/or PTEN expression loss) had a lower clinical benefit rate (36.4% versus 68.6%, P = 0.017) and a lower overall response rate (9.1% versus 31.4%, P = 0.05), when compared with the 35 patients with no activation. A retrospective analysis of first trastuzumab-containing regimen treatment data showed that PI3K pathway activation correlated with a shorter median progression-free survival (4.5 versus 9.0 months, P = 0.013). PIK3CA mutations occur more frequently in elder patients for HER2-positive breast cancer. PIK3CA mutations and PTEN loss are not mutually exclusive. PI3K pathway activation resulting from PTEN loss or PIK3CA mutations may lead to drug resistance to lapatinib and trastuzumab.
    BMC Cancer 06/2011; 11:248. · 3.33 Impact Factor
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    ABSTRACT: Angiogenesis is an important process in cell development, especially in cancer. Vascular endothelial growth factor (VEGF) signaling is an important regulator of angiogenesis. Several therapies that act against VEGF signal transduction have been developed, including YN968D1, which is a potent inhibitor of the VEGF signaling pathway. This study investigated the antitumor activity of YN968D1 (apatinib mesylate) in vitro and in vivo. YN968D1 potently suppressed the kinase activities of VEGFR-2, c-kit and c-src, and inhibited cellular phosphorylation of VEGFR-2, c-kit and PDGFRβ. YN968D1 effectively inhibited proliferation, migration and tube formation of human umbilical vein endothelial cells induced by FBS, and blocked the budding of rat aortic ring. In vivo, YN968D1 alone and in combination with chemotherapeutic agents effectively inhibited the growth of several established human tumor xenograft models with little toxicity. A phase I study of YN968D1 has shown encouraging antitumor activity and a manageable toxicity profile. These findings suggest that YN968D1 has promise as an antitumor drug and might have clinical benefits.
    Cancer Science 03/2011; 102(7):1374-80. · 3.48 Impact Factor
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    ABSTRACT: YN968D1 (Apatinib) selectively inhibits phosphorylation of VEGFR-2 and tumor angiogenesis in mice model. The study was conducted to determine the maximum tolerated dose (MTD), safety profile, pharmacokinetic variables, and antitumor activity in advanced solid malignancies. This dose-escalation study was conducted according to the Chinese State Food and Drug Administration (SFDA) recommendations in patients with advanced solid tumors to determine the MTD for orally administered apatinib. Doses of continuously administered apatinib were escalated from 250 mg. Treatment continued after dose-escalation phase until withdrawal of consent, intolerable toxicities, disease progression or death. Forty-six patients were enrolled. Hypertension and hand-foot syndrome were the two dose-limiting toxicities noted at dose level of 1000 mg. MTD was determined to be 850 mg once daily. Pharmacokinetic analysis showed early absorption with a half-life of 9 hours. The mean half-life was constant over all dose groups. Steady-state conditions analysis suggested no accumulation during 56 days of once-daily administration. The most frequently observed drug-related adverse events were hypertension (69.5%, 29 grade 1-2 and 3 grade 3-4), proteinuria (47.8%, 16 grade 1-2 and 6 grade 3-4), and hand-foot syndrome (45.6%, 15 grade 1-2 and 6 grade 3-4). Among the thirty-seven evaluable patients, PR was noted in seven patients (18.9%), SD 24 (64.9%), with a disease control rate of 83.8% at 8 weeks. The recommended dose of 750 mg once daily was well tolerated. Encouraging antitumor activity across a broad range of malignancies warrants further evaluation in selected populations. ClinicalTrials.gov unique identifier: NCT00633490.
    BMC Cancer 10/2010; 10:529. · 3.33 Impact Factor
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    ABSTRACT: Zoledronic acid has direct and indirect antitumor effects. However, the optimal regimen for breast cancer patients remains to be determined. This study aimed to compare biomarker changes between a weekly low dose (metronomic arm) and a conventional dosage of zoledronic acid (conventional arm), and to explore correlations between biomarkers and progression-free survival (PFS). Sixty breast cancer patients with bone metastases were randomized to receive either zoledronic acid 1 mg IV weekly for 4 doses or a single dose of zoledronic acid 4 mg IV. Administration of other treatments was delayed for 1 month. Serial blood samples were collected on days 1, 15, 29, and at 3 months. Serum VEGF alteration was the primary endpoint. Compared to the conventional arm, the metronomic arm resulted in a significantly greater reduction in serum levels of VEGF and N-telopeptide of type I collagen (NTx) over time during the first month of treatment. Serum CA 15-3 level stabilized over time in the metronomic arm, but increased in the conventional arm. Independent prognostic factors for PFS included chemotherapy received (HR, 8.042; P = 0.000), estrogen receptor status (HR, 2.837; P = 0.020), VEGF levels at 3 months after intervention (HR, 2.026; P = 0.045), and baseline NTx (HR, 1.051; P = 0.001). Metronomic low-dose zoledronic acid is more effective than the conventional regimen and generates sustained reductions in circulating VEGF and NTx levels, as well as stabilization of serum CA 15-3 levels (ClinicalTrials.gov number, NCT00524849).
    Breast Cancer Research and Treatment 09/2010; 124(3):733-43. · 4.47 Impact Factor
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    ABSTRACT: ObjectiveIt remains unclear whether simultaneous use of two chemotherapeutic drugs is better than sequential use. This trial was designed to explore efficacy and safety of sequential vs simultaneous use of vinorelbine and capecitabine at the same dosage as first-line therapy in metastatic breast cancer (MBC). MethodsThis was a un-icenter, randomized phase II trial. Patients randomized into the simultaneous group (group A) were simultaneously administered with vinorelbine and capecitabine while those in the sequential group (group B) received vinorelbine followed by capecitabine at the same dosage. ResultsSixty-six patients were screened and 30 patients were randomized into either group. There’re significant differences in the clinical benefit rate (CBR) with 80.0% for group A vs 53.3% for group B (P = 0.028). With a median follow up time of 13.5 months, there were no significant differences between the two groups in PFS (median PFS: 7.70 months for group A vs 7.23 months for group B, P = 0.436). Grade III or IV neutropenia (83.3% vs 50.0%, P = 0.006), all grades of fatigue (56.7% vs 30.0%, P = 0.037) and anorexia (53.3% vs 23.3%, P = 0.017) were significantly more frequent in simultaneous group. ConclusionSimultaneous administration of vinorelbine and capecitabine can bring about improvements in CBR, but cannot translate into long-term benefits, such as progression-free survival (PFS) or overall survival (OS). These findings, combined with a relatively better tolerability in sequential group, showed that both simultaneous and sequential administrations are reasonable options for MBC patients. Key wordsvinorelbine-capecitabine-simultaneous administration-sequential administration-metastatic breast cancer (MBC)-phase II clinical trial
    The Chinese-German Journal of Clinical Oncology 01/2010; 9(9):528-535.
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    ABSTRACT: KH901 is a conditionally replicating oncolytic adenovirus, which reported selectively replicates in and lyses telomerase-positive tumor cells and expresses granulocyte macrophase colony-stimulating factor (GM-CSF). To determine the safety, feasibility and biological activity of KH901, a conditionally replicating oncolytic adenovirus, in patients with recurrent head and neck cancer (HNC). Treatment was well tolerated, with the main toxicity being grade 1/2 flu-like symptoms. Dose-limiting toxicity was not reached in either single dose groups or multiple dose groups. KH901 was detected in urine, but little was found in feces. Interestingly, a second peak of detectable KH901 genome found in the circulation in majority of patients tested between 2 and 4 days after treatment. High level of GM-CSF in circulation was detected in all single dose patients 12 h and became undetectable 15 days following injection. All 23 patients treated showed an increase in neutralizing antibody to adenovirus. Twenty-three patients with recurrent HNC was administered by intratumoral injection in two parts of trial. In the single dose escalating portion, four cohort of 13 patients received a single injection of KH901 at a dose of 3 x 10(11) virus particle (vp), 1 x 10(12) vp, 3 x 10(12) vp and 1 x 10(13) vp, respectively, while in the multiple dose portion each cohort of six patients received twice weekly a total of six injections at a dose of either 1 x 10(12) vp or 3 x 10(12) vp. Toxicity was assessed using NCIC criteria. Tumor response was assessed by clinical and radiological measurement. Blood samples were taken to detect adenovirus DNA, GM-CSF expression and neutralizing antibody to adenovirus. These preliminary results showed that intratumoral administration of KH901 was feasible, well tolerated and associated with biological activity, further investigation of KH901, particularly in combination with systemic chemotherapy, was warranted.
    Cancer biology & therapy 05/2009; 8(8):676-82. · 3.29 Impact Factor
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    ABSTRACT: ObjectiveThe mitomycin C and cisplatin combination was investigated in patients with advanced breast cancer who had been exposed to anthracyclines, vinorelbine and taxanes. MethodsThree-weekly regimen consisted of mitomycin, 6 mg/m2 administered intravenously on day 1, and cisplatin, 25 mg/m2 intravenously on day 1–3. ResultsThirty-eight patients aged 25–75 years (median, 46 years) were treated with an overall response rate of 31.6%. The median time to progression (TTP) was 4.0 months. Median TTP for 12 patients with a complete or partial response was 9.0 months, while stable disease and progression of disease 4.0 months, P=0.002. Grade 3/4 side effects of neutropenia, thrombocytopenia and nausea/vomiting were documented in 4 (10.5%), 4 (10.5%) and 3 (7.9%) patients, respectively. The median overall survival was 13+ months. ConclusionMitomycin C/cisplatin doublet showed antitumor activity for anthracycline-, vinorelbine-and taxane-resistant breast cancer comparable to other regimens. This well-tolerated regimen provides an affordable option for patients in China.
    The Chinese-German Journal of Clinical Oncology 01/2006; 5(6):442-445.