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Diagnostic challenges and individualized treatment of cervical adenocarcinoma metastases to the breast:A case report

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World Journal of Clinical Cases 2024年第2期12卷 412-417页

作者： Allison Akers Susan Read John Feldman Casey Gooden Diana P English Department of Obstetrics and Gynecology University of South FloridaTampaFL 33606United States Department of Gynecologic Oncology Sky Ridge Medical CenterLone TreeCO 80124United States Department of Radiology University of South FloridaTampaFL 33606United States Department of Pathology University of South FloridaTampaFL 33606United States

BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.

关键词： Cervical adenocarcinoma Breast metastases Immunotherapy Pembrolizumab carboplatin Paclitaxel Case report

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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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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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Efficacy and feasibility of gemcitabine and carboplatin as first-line chemotherapy in elderly patients with advanced non-small cell lung cancer

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Chinese Medical Journal 2013年第24期126卷 4644-4648页

作者： Kyu-Hyoung Lim Hui-Young Lee Seo-Young Song Department of Internal Medicine Kangwon National UniversityHospital Kangwon National University School of Medicine 17-1Hyoja 3-dong Chuncheonsi Gangwon-do 200-947 South Korea

Background Although platinum-based chemotherapy is a standard first-line treatment in advanced non-small cell lung cancer （NSCLC）, further research for the safety and efficacy of combination chemotherapy in elderly patients has been required. The purpose of this study was to evaluate the efficacy and safety of gemcitabine and carboplatin as first-line treatment in elderly patients with advanced NSCLC and to evaluate the prognostic factors. Methods Eligibility included：（1） age of 70 years or more, （2） histologically confirmed NSCLC, （3） chemotherapy-na＇l＇ve, （4） advanced disease with stage IIIB or IV, （5） Eastern Cooperative Oncology Group （ECOG） performance status （PS） 0-2, （6） adequate organ function. Patients received intravenous carboplatin （area under curve （AUC）=5） on day 1 and gemcitabine （1000 mg/m2） on days 1 and 8, every 3 weeks. Results The medical records of forty patients were reviewed retrospectively. Median age was 73.9 years （range, 70- 84.6）, and there were 27 men （67.5%）. Thirty-seven patients （92.5%） had ECOG PS 0-1. Adenocarcinoma was found in 57.5%. Median cycles were administrated with 4.5 per person （range： 1-6）. Best responses were partial response in 22 （55.0%） patients and stable disease （SD）in 13 （32.5%）. The median progression free survival （PFS） and overall survival （OS） were 5.9 months （95% CI： 4.5-7.3 months） and 9.6 months （95% CI： 8.2-11.0 months）, respectively. Grade 4 hematologic toxicities for neutropenia （7.5%）, thrombocytopenia （7.5%） and anemia （5.0%） were observed. Histology was significant prognostic factor for PFS （P=0.024）. Conclusion Gemcitabine and carboplatin combination chemotherapy is an effective and manageable treatment option in elderly advanced NSCLC patients with good performance status.

关键词： gemcitabine carboplatin elderly, non-small cell lung cancer

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Dose-dense paclitaxel plus carboplatin vs.epirubicin 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 surgery.They 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)support.The primary endpoint was 3-year disease-free survival(DFS);the secondary endpoints were overall survival(OS)and safety.Results: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 OS.PCdd also yielded lower hematological toxicity.Thus,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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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 delivery.CBP/SB-NC was prepared by co-loading CBP and NaHCO 3(SB)in nanocapsules using w/o/w emulsification solvent evaporation.They exhibited vesicle-like spherical morphology,uniform particle size and negative zeta potential.Reaching 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 site.After 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 solution.After internalized by RM-1 cells,the gas-blasting release process was tested in acid environment.It was demonstrated that 5 mg/ml NaHCO 3 was optimal to achieve pH-responsive gas-blasting release.In 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 cytoplasm.Furthermore,the nucleus delivery results showed CBP/SB 5-NC can promote pH-triggered rapid nucleus delivery.And 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 solution.At last,in vitro and in vivo anti-tumor efficacy proved that CBP/SB 5-NC could enhance anti-tumor activity for prostate cancer therapy.CBP/SB 5-NC also showed superior safety in vitro and in vivo by hemolysis assay and histopathological study.All of the results demonstrate that CBP/SB 5-NC would be an efficient gas-blasting release formulation to enhance prostate cancer treatment.

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

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Resistance to cis- and carboplatin initiated by epigenetic changes in ovarian cancer patients

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Cancer Drug Resistance 2019年第2期2卷 271-296页

作者： Heidi Schwarzenbach Peter B.Gahan Department of Tumor Biology University Medical Center Hamburg-EppendorfHamburg 20246Germany Fondazione“Enrico Puccinelli”Onlus Perugia 06126Italy

Initially,most ovarian tumors respond to the treatment with platinum components,but frequently recurrence occurs within the following two years in advanced ovarian cancer patients.In this regard,previous studies have shown changes in the epigenetic patterns in ovarian cancer that are linked with resistance to cis-and carboplatin therapy.Thus,epigenetic changes mediated by a treatment with cis-or carboplatin could identify such patients who do or do not respond to this therapy.Therefore,an understanding of the impact of platinum on epigenetics in ovarian cancer is important in overcoming platinum resistance.In this review,we delineate epigenetic abnormalities in cis-and carboplatin-resistant ovarian tumors,such as changes in DNA methylation,histone modifications and deregulation of microRNAs,and discuss the potential of epigenetic therapies in combination with platinum.

关键词： Ovarian cancer carboplatin cisplatin resistance DNA methylation histone modifications microRNAs

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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 havebeen studied at 313 and 254 nm irradiation.Excitation in the ligand field bands 1A1→1A2 and 1A1→1E leads tosubstitution reactions,giving diaquodiammineplatinum and tetraaquoplatinum.And then these complexesundergo thermally hydrolysis and polymerization producing polymeric hydroxo-bridged complexes.Oxygen isnot involved in the reactions.Excitation in the charge-transfer band 1A1→1A2u results in redox reaction.Metallic platinum and diaquodiammineplatinum are formed,respectively,in the absence and the presence ofoxygen.

关键词： carboplatin complex photochemistry anticancer

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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 present at the highest dose, 5 mM. Unlike the nonli

关键词： carboplatin ototoxicity organotypic culture

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A phase Ⅱ study of gemcitabine and carboplatin combination chemotherapy in gallbladder carcinoma

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Hepatobiliary & Pancreatic Diseases International 2006年第1期5卷 110-114页

作者： Pramod Kumar Julka Tarun Puri Goura Kishore Rath Department of Radiotherapy & Oncology

BACKGROUND: Patients with carcinoma of the gallbladder have advanced, unresectable tumor at the time of presentation and face a dismal prognosis in the absence of a standard palliative chemotherapy regimen. This study was undertaken to evaluate the efficacy and safety of combined chemotherapy of gemcitabine and carboplatin in 20 patients with advanced gallbladder carcinoma. METHODS: The criteria of eligibility included chemonaive patients with unresectable gallbladder cancer, bidimensionaIly measurable disease, Zubrod's performance status≤2, and adequate major organ function. The patients received gemcitabine (1000 mg/m^2) on days 1 and 8, and carboplatin (target AUC of 5.0 mg/ml) on day 1, in a 21-day cycle. CT was used for response assessment. RESULTS: In this group of 20 patients with advanced gallbladder carcinoma 6 were men and 14 women, with a median age of 55 years. The stage of the tumor at presentation was IVB in 14 patients (70%), IVA in 3 (15%) and Ⅲ in 3 (15%). Four patients (21%) achieved a complete response, and 3 (15.7%), a partial response; an overall response rate was 36.7%. The median time to progression of the tumor was 33.8 weeks, and 1-year survival rate of the patients was 43.3%. Anemia of WHO grade Ⅲ or Ⅳ was seen in 2 patients (10%) and 1 patient (5%), respectively. Grade Ⅲ neutropenia and thrombocytopenia were observed in 2 patients (10%) and 1 patient (5%), respectively. CONCLUSION: With mild toxicity, combined chemotherapy of gemcitabine and carhoplatin is effective in the treatment of advanced gallbladder carcinoma.

关键词： gallbladder cancer gemcitabine carboplatin

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