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Association between HER2 status and response to neoadjuvant anthracycline followed by paclitaxel plus carboplatin chemotherapy without trastuzumab in breast cancer

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Chinese Journal of Cancer Research 2015年第6期27卷 553-561页

作者： Lu Yao Juan Zhang Yiqiang Liu Tao Ouyang Jinfeng Li Tianfeng Wang Zhaoqing Fan Tie Fan Benyao Lin Yuntao Xie Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Breast Center Beijing Cancer Hospital & Institute Peking University Cancer Hospital Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Pathology Beijing Cancer Hospital & Institute Peking University Cancer Hospital

Background： We recently showed HER2-positive breast cancers are less likely to respond to neoadjuvant anthracycline chemotherapy. Here, we investigated whether HER2-positive breast cancers responded to sequential neoadjuvant anthracycline followed by paclitaxel plus carboplatin regimen in the absence of trastuzumab. Methods： Women （n=372） with operable primary breast cancer initially received two cycles of neoadjuvant anthracyclines, the clinical tumor response was assessed, then patients were received four cycles of paelitaxel plus carboplatin regimen. All the patients did not received trastuzumab treatment in the neoadjuvant setting. HER2 status was determined by immunohistochemistry and/or by fluorescence in situ hybridization in core- biopsy breast cancer tissue obtained before the neoadjuvant chemotherapy. Results： Eighteen percent （67/372） of patients achieved a pathologic complete response （pCR） in their breast. HER2-positive tumors had a significant higher pCR rate than HER2-negative tumors （33.0% versus 13.5%, P〈0.001） in this cohort of 372 patients, and positive HER2 status remained an independent favorable predictor of pCR in a multivariate analysis [odds ratio （OR）, 2.26; 95% confidence interval （CI）, 1.18 to 4.36, P=0.015]. Furthermore, patients who responded to initial anthracycline regimens were more likely to respond to paclitaxel plus carboplatin than patients who did not （pCR, 27.2% versus 14.6%, P=0.005）. Patients with HER2-positive tumors exhibited a significant higher pCR rate than did patients with HER2- negative tumors in both anthracycline response group （40.5% versus 20.0%, P=0.025） and anthracycline non-response group （28.3% versus 11.3 %, P=0.002）. Conclusions： Under the circumstance of no trastuzumab treatment, women with HER2-positive cancers derive a large benefit from paclitaxel-carboplatin-based neoadjuvant chemotherapy.

关键词： HER2 breast cancer neoadjuvant chemotherapy paclitaxel carboplatin

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Effect of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid in combination with carboplatin on gastric carcinoma growth in vivo

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World Journal of Gastroenterology 2007年第4期13卷 509-514页

作者： Jin-Lian Chen Jin-Shui Zhu Jing Hong Ming-Xiang Chen Jin-Lai Lu Wei-Xiong Chen Bo Shen Zu-Ming Zhu Ni-Wei Chen Department of Gastroenterology Shanghai Sixth People's Hospital Shanghai Jiaotong University Shanghai 200233 China

AIM： To investigate the effects of 2-（8-hydroxy-6- methoxy-l-oxo-lH-2-benzopyran-3-yl） propionic acid （NM-3） alone and in combination with carboplatin on tumor growth and apoptosis in mouse models of human gastric cancer constructed by subcutaneous implantation of histologically intact tumor tissue. METHODS： Human gastric cancer SGC-7901 tissues were implanted into the dorsal subcutis of nude mice. One week after tumors reached to a volume of 50-100 mm3 for around 1 wk, these mice were randomly divided into 8 groups （n = 10）. NM-3 was injected peritoneally at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg every other day for 5 wk, combined with carboplatin （5 mg/kg） every third day for 4 wk. As controls of combined treatment, another 4 groups of mice were injected with either NM-3 at 10 mg/kg, 20 mg/kg or 40 mg/kg, or with carboplatin alone （5 mg/kg）. The control mice received normal saline. Tumor weight, tumor growth inhibition （TGI）, and intratumoral microvessel density （MVD） were evaluated. Apoptosis of human gastric cancer was detected by TUNEL method and flow o/tometry analysis, respectively. RESULTS： The mean tumor volume （692.40 ± 58.43 mm3, 548.30 ± 66.02 mm3, 382.13 ± 43.52 mm3） after treatment with carboplatin combined NM-3 at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg was lower than that after treatment with either NM-3 at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg or with carboplatin alone. Compared with the normal saline group, NM-3 administered at 10 mg/kg, 20 mg/kg or 40 mg/kg significantly reduced the tumor weight in these groups （P 〈 0.05）. carboplatin used alone at 5 mg/kg showed minimal effects. But NM-3 in combination with carboplatin had greater effects of tumor weight than either NM-3 or carboplatin alone. NM-3 alone at the dose 10 mg/kg or in combination with carboplatin had no obvious effects on body changes. Two mice died of diarrhea in each of the two groups treated with 40 mg/kg NM-3 or with 40 mg/kg NM-3 in combination with carboplatin. A

关键词： NM-3 carboplatin Gastric carcinoma Angiogenesis Apoptosis

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Nedaplatin/Gemcitabine Versus carboplatin/Gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial

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Chinese Journal of Cancer Research 2012年第2期24卷 97-102页

作者： Jin-ji Yang Qing Zhou Ri-qiang Liao Yi-sheng Huang Chong-rui Xu Zhen Wang Bin-chao Wang Hua-jun Chen Yi-long Wu Division of Pulmonary Oncology Guangdong Lung Cancer InstituteCancer CenterGuangdong General Hospital&Guangdong Academy of Medical SciencesGuangzhou 510080China

Objective： To evaluate the efficacy and safety of nedaplatin/gemcitabine （NG） and carboplatin/gemcitabine （CG） in the management of untreated advanced non-small cell lung cancer （NSCLC）. Methods： Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm （n=30） and the CG arm （n=32）. Only patients （24 and 25 in the NG and CG arms, respectively） who completed 〉2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate （ORR）. The secondary outcome measures included progression-free survival （PFS）, overall survival （OS） and adverse events. Results： There were no statistically significant differences in the efficacy measures （ORR, P=0.305; median PFS, P=0.298, median OS, P=0.961） or in the major adverse events （grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.222） between the two treatment arms. However, there was a trend towards higher ORR （37.5% vs. 24.0%）, longer PFS （6.0 vs. 5.0 months）, and less adverse events in the NG arm. Conclusion： NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.

关键词： Non-small cell lung cancer Chemotherapy Nedaplatin carboplatin Gemcitabine Squamous cell carcinoma

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Photochemical Studies on Aqueous carboplatin

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Science China Chemistry 1994年第7期37卷 799-806页

作者：刘伟平杨懿昆阙振寰熊惠周 Institute of Precious Metals

The photochemical products,quantum yields and mechanisms of aqueous carboplatin have been studied at 313 and 254 nm *** in the ligand field bands ~1A_1→~1A_2 and ~1A_1→~1E leads to substitution reactions,giving diaquodiammineplatinum and *** then these complexes undergo thermally hydrolysis and polymerization producing polymeric hydroxo-bridged *** is not involved in the *** in the charge-transfer band ~1A_1→~1A_(2u) results in redox reaction. Metallic platinum and diaquodiammineplatinum are formed,respectively,in the absence and the presence of oxygen.

关键词： carboplatin complex photochemistry anticancer

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Gas-blasting nanocapsules to accelerate carboplatin lysosome release and nucleus delivery for prostate cancer treatment

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Asian Journal of Pharmaceutical Sciences 2021年第2期16卷 192-202页

作者： Shunli Fu Shuang Liang Dandan Jiang Rui Yang Zipeng Zhang Lili Chang Xinke Zhang Yongjun Liu Na Zhang Department of Pharmaceutics Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJinan 250012China

To improve therapeutic effect and reduce severely side effects of carboplatin(CBP),the gas-generating nanocapsules were developed to accelerate CBP lysosome release and nucleus ***/SB-NC was prepared by co-loading CBP and NaHCO 3(SB)in nanocapsules using w/o/w emulsification solvent *** exhibited vesicle-like spherical morphology,uniform particle size and negative zeta *** the tumor site with a relatively high concentration is the first step for CBP delivery and the results showed that CBP/SB-NC could effectively increase drug accumulation at tumor *** that,the drug delivery carriers need to be internalized into tumor cells and the in vitro cellular uptake ability results showed CBP/SB-NC could be internalized into RM-1 cells more efficient than CBP *** internalized by RM-1 cells,the gas-blasting release process was tested in acid *** was demonstrated that 5 mg/ml NaHCO 3 was optimal to achieve pH-responsive gas-blasting *** vitro release results showed that CBP significantly rapid release in acid environment(pH 5.0)compared to neutral pH(pH 7.4)(P<0.05).Meanwhile,TEM and the change of the concentration of H+results exhibited that the explosion of CBP/SB 5-NC was more easily happened in lysosome acid environment(pH 5.0).The blasting release can accelerate CBP lysosome release to ***,the nucleus delivery results showed CBP/SB 5-NC can promote pH-triggered rapid nucleus *** the results of Pt-DNA adduct assay showed that the binding efficiency between CBP and DNA of CBP/SB 5-NC was higher than CBP *** last,in vitro and in vivo anti-tumor efficacy proved that CBP/SB 5-NC could enhance anti-tumor activity for prostate cancer ***/SB 5-NC also showed superior safety in vitro and in vivo by hemolysis assay and histopathological *** of the results demonstrate that CBP/SB 5-NC would be an efficient gas-blasting release formulation to enhance prostate cance

关键词： carboplatin Nanocapsule pH-responsive release Gas-blasting Prostate cancer

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Dose-dense paclitaxel plus carboplatin *** and cyclophosphamide with paclitaxel as adjuvant chemotherapy for high-risk triple-negative breast cancer

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Chinese Journal of Cancer Research 2020年第4期32卷 485-496页

作者： Qing Li Jiani Wang Yuxin Mu Tongtong Zhang Ying Han Jiayu Wang Qiao Li Yang Luo Fei Ma Ying Fan Pin Zhang Binghe Xulj Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective:The objective of this open-label,randomized study was to compare dose-dense paclitaxel plus carboplatin(PCdd)with dose-dense epirubicin and cyclophosphamide followed by paclitaxel(ECdd-P)as an adjuvant chemotherapy for early triple-negative breast cancer(TNBC).Methods:We included Chinese patients with high recurrence risk TNBC who underwent primary breast cancer *** were randomly assigned to receive PCdd[paclitaxel 150 mg/m2 on d 1 and carboplatin,the area under the curve,(AUC)=3 on d 2]or ECdd-P(epirubicin 80 mg/m2 divided in 2 d and cyclophosphamide 600 mg/m2 on d 1 for 4 cycles followed by paclitaxel 175 mg/m2 on d 1 for 4 cycles)every 2 weeks with granulocyte colony-stimulating factor(G-CSF)*** primary endpoint was 3-year disease-free survival(DFS);the secondary endpoints were overall survival(OS)and ***:The intent-to-treat population included 143 patients(70 in the PCdd arm and 73 in the ECdd-P arm).Compared with the ECdd-P arm,the PCdd arm had significantly higher 3-year DFS[93.9%vs.79.1%;hazard ratio(HR)=0.310;95%confidence interval(95%CI),0.137-0.704;log-rank,P=0.005]and OS(98.5%vs.92.9%;HR=0.142;95%CI,0.060-0.825;log-rank,P=0.028).Worse neutropenia(grade 3/4)was found in the ECdd-P than the PCdd arm(47.9%V5.21.4%,P=0.001).Conclusions:PCdd was superior to ECdd-P as an adjuvant chemotherapy for early TNBC with respect to improving the 3-year DFS and *** also yielded lower hematological ***,PCdd might be a preferred regimen for early TNBC patients with a high recurrence risk.

关键词： Triple-negative breast cancer dose-dense adjuvant chemotherapy carboplatin paclitaxel

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PACLITAXEL PLUS carboplatin FOR WOMEN WITH ADVANCED BREAST CANCER

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Chinese Medical Sciences Journal 2007年第2期22卷 93-97页

作者： Ju Liu Qing Li Pin Zhang Jia-yu Wang Long-mei Zhao Bing-he Xu Department of Medical Oncology Cancer Hospital ＆ Institute Chinese Academy of Medical Sciences ＆Peking Union Medical College Beijing 100021

Objective To evaluate the efficacy and safety of combination chemotherapy with paclitaxel and carboplatin for advanced breast cancer (ABC). Methods From January 2001 to March 2006, 45 patients with ABC were treated with combination chemotherapy of paclitaxel and carboplatin. Patients received infusion of paclitaxel 175 mg/m2 on day 1 every 3 weeks or 75 mg/m2 on day 1, 8, 15 every 4 weeks. carboplatin was administrated on day 2 with a dose of area under the time-concentration curve (AUC) being 5. Results The median number of cycles was 3 (range, 2-6). The overall response rate was 62.2%. Median time to progression was 7.0 months (95%CI:5.1-8.9). Median overall survival was 29.0 months (95%CI: 20.1-37.9). One year survival rate was 73.3%. Response rate for first line and second line treatment were 62.1% and 62.5%, respectively. No significant difference in response existed between visceral metastasis and soft tissue metastasis. The main side effects included nausea/vomiting, neurotoxicity, and hematologic toxicities. Grade Ⅲ to Ⅳ adverse events included nausea/vomiting in 2 cases (4.4%), leukopenia in 17 cases (37.8%), and alopecia in 6 cases (13.3%). Conclusion Combination of paclitaxel and carboplatin is active in treatment of ABC with an acceptable toxicity profile.

关键词： breast neoplasms paclitaxel carboplatin

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OTOTOXIC EFFECTS OF carboplatin IN ORGANOTYPIC CULTURES IN CHINCHILLAS AND RATS

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Journal of Otology 2012年第2期7卷 92-101页

作者： DING Dalian JIANG Haiyan FU Yong Richard SALVI Shinichi SOMEYA Masaru TANOKURA Center for Hearing and Deafness State University of New York at Buffalo Graduate School of Agricultural and Life Sciences University of Tokyo Departments of Aging and Geriatric Research Division of Biology of Aging University of Florida

carboplatin, a second-generation platinum chemotherapeutic drug, is considerably less ototoxic than cisplatin. While common laboratory species such as mice, guinea pigs and rats are highly resistant to carboplatin ototoxicity, the chinchilla stands out as highly susceptible. Moreover, carboplatin causes an unusual gradient of cell death in chinchillas. Moderate doses selectively damage type I spiral ganglion neurons (SGN) and inner hair cells (IHC) and the lesion tends to be relatively uniform along the length of the cochlea. Higher doses eventually damage outer hair cells (OHC), but the lesion follows the traditional gradient in which damage is more severe in the base than the apex. While carboplatin ototoxicity has been well documented in adult animals in vivo, little is known about its in vitro toxicity. To elucidate the ototoxic effects of carboplatin in vitro, we prepared cochlear and vestibular organotypic cultures from postnatal day 3 rats and adult chinchillas. Chinchilla cochlear and vestibular cultures were treated with carboplatin concentrations ranging from 50 μM to 10 mM for 48 h. Consistent with in vivo data, carboplatin selectively damaged IHC at low concentrations (50-100 μM). Surprisingly, IHC loss decreased at higher doses and IHC were intact at doses exceeding 500 μM. The mechanisms underlying this nonlinear response are unclear but could be related to a decrease in carboplatin uptake via active transport mechanisms (e.g., copper). Unlike the cochlea, the carboplatin dose-response function increased with dose with the highest dose destroying all chinchilla vestibular hair cells. Cochlear hair cells and auditory nerve fibers in rat cochlear organotypic cultures were unaffected by carboplatin concentrations <10 μM; however, the damage in OHC were more severe than IHC once the dose reached 100 μM. A dose at 500 μM destroyed all the cochlear hair cells, but hair cell loss decreased at high concentrations and nearly all the cochlear hair cells were pre

关键词： carboplatin ototoxicity organotypic culture

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A logarithmic rapid desensitization protocol: initial experience in carboplatin hypersensitivity reactions

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Journal of Cancer Metastasis and Treatment 2019年第8期4卷 21-28页

作者： Enrique Burches Jose-Alejandro Pérez-Fidalgo Francisco Ferriols Inés González-Barrallo AndrésCervantes Allergy Department Hospital Clinico UniversitarioValencia 46010Spain Oncology Department Hospital Clinico Universitario and INCLIVA Research InstituteValencia 46010Spain Pharmacy Department Hospital Clinico UniversitarioValencia 46010Spain

Aim: Hypersensitivity reactions to carboplatin are not an infrequent adverse event in ovarian cancer patients. However, reintroduction of platinum-containing schedules is the standard of care in platinum-sensitive recurrent ovarian cancer. Rapid desensitization is a procedure for gradual reintroduction of drug. It allows a safe administration of medications that are beneficial for the management of patients after certain types of hypersensitivity reactions. It is indicated in cases in which there are no reasonable therapeutic alternatives. Methods: We performed a descriptive retrospective study of high-grade ovarian cancer patients with known carboplatin hypersensitivity reactions that were treated with a 13-steps rapid desensitization protocol with 3 different solutions and infusion rates. The procedure followed a mathematic model (gradual increases with a relationship between doses following a geometric series) which is called logarithmic rapid desensitization protocol (LRDP). The aim was to describe the safety of the LRDP in terms of number and severity of infusion reactions and the effectiveness in the rate of cycles completely administered. Results: Four different patients diagnosed with recurrent platinum-sensitive ovarian cancer with a previous infusion reaction were included. LRDP was administered in 19 different cycles. LRDP was administered safety in all 19 cycles, only 2 patients had a mild cutaneous reaction in 4 different cycles during LRDP (21.05%). The foreseen dose of carboplatin was fully administered in all ***: LRDP with carboplatin is a feasible and safe protocol in patients with previous infusion reaction to carboplatin. The protocol might allow a safe administration of drugs, that are beneficial for the management of patients, after certain types of hypersensitivity reactions, and it is indicated in cases in which there are no reasonable therapeutic alternatives.

关键词： Drug allergy hypersensitivity desensitization rapid protocol logarithmic model carboplatin

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EFFECT OF NEOADJUVANT CHEMOTHERAPY USING PACLITAXEL COMBINED WITH carboplatin ON ADVANCED NON-SMALL CELL LUNG CANCER

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Chinese Journal of Cancer Research 2006年第3期18卷 218-221页

作者：熊宏超陈晋峰张力建 Department of Surgical Oncology Peking University School of Oncology Beijing Cancer Hospital Beijing Institute for Cancer Research Beijing 100036

Objeetive： To assess the therapeutic effectiveness of preoperative neoadjuvant chemotherapy using a combination of paclitaxel and carboplatin on local advanced non-small cell lung cancer （NSCLC）. Methods： Twenty-five patients with advanced NSCLC were treated with paclitaxel and carboplatin for 2 to 4 cycles before undergoing tumor resection and then postoperative chemotherapy/radiotherapy therapy for 2 to 4 cycles. Results： Following neoadjuvant chemotherapy, the most prominent side-effect was bone marrow restraint. The overall response rate of preoperative chemotherapy was 56%. The mean survival time was 26.5 months, with 1-, 2- and 5-year survival rates of 55%, 25%, and 16%, respectively. All NSCLC patients survived the perioperative period. Conclusion： Preoperative neoadjuvant chemotherapy combining paclitaxel and carboplatin produced minimal side-effect while increasing the probability that advanced NSCLC patients would be able to undergo surgery thus improving their prognosis.

关键词： Paclitaxel carboplatin Neoadjuvant chemotherapy Advanced lung cancer

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