• Title/Summary/Keyword: Carboplatin

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Salvage Chemotherapy in Recurrent Platinum-Resistant or Refractory Epithelial Ovarian Cancer with Carboplatin and Distearoylphosphatidylcholine Pegylated Liposomal Doxorubicin (Lipo-Dox®)

  • Khemapech, Nipon;Oranratanaphan, S.;Termrungruanglert, W.;Lertkhachonsuk, R.;Vasurattana, A.
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.2131-2135
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    • 2013
  • Background: To evaluate the efficacy and safety of distearoylphosphatidylcholine pegylated liposomal doxorubicin (DPLD) combined with carboplatin for the treatment of platinum resistant or refractory epithelial ovarian cancer (EOC) or fallopian tube cancer. Materials and Methods: A retrospective analysis of women who received DPLD with carboplatin for recurrent EOC or fallopian tube cancer in King Chulalongkorn Memorial Hospital Thailand from January 2006 to August 2011 was conducted. Patients were identified from the medical records and data on demographic factors, stage, histology, surgical findings, cytoreduction status, and prior chemotherapies were abstracted. The efficacy and toxicity of DPLD/carboplatin were evaluated. Progression-free (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: A total of 65 patients, 64 with platinum resistant or refractory epithelial ovarian cancer and 1 with fallopian tube cancer, were enrolled. DPLD and carboplatin were given for an average of 4.46 cycles per patient with a total of 273 cycles. Among the 65 evaluable patients, 0% achieved CR, 7.69% PR, 15.4% SD and 76.% PD. The overall response rate was 23.1%. With a median follow-up of 27.4 months, the median progression-free and median overall survival in the 36 patients was 4.46 months and 8.76 months respectively. In the aspect of side effects, palmar-plantar erythrodysesthesia (PPE) occurred in 33.3% (Grade I 22.2%, Grade II 11.1%) and mucositis in 41.7% (Grade I 27.8%, Grade II 13.9%) of all treatment cycles, all Grade 1 or 2. Anemia, leukopenia and thrombocytopenia occurred in 58.3% (Grade I 41.7%, Grade II 16.7%), 66.7% (Grade I 47.2%, Grade II 19.4%), and 22.2% (Grade I 16.6%, Grade II 5.56%) of cycle respectively, and were mostly Grade 1 or 2. Conclusions: DPLD, the second-generation PLD drug combined with carboplatin every 4 weeks, is effective and has low toxicity for treatment of patients with recurrent platinum-resistant or refractory epithelial ovarian cancer.

Comparative Pharmacokinetics of Platinum Coordination Complexes in Rats

  • Insook Jung;Lee, Juseon;Kim, Myungsoo;Changbae Jin;Younsoo Sohn;Park, Jongsei
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.243-243
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    • 1996
  • 백금착물 항암제 후보물질로서 합성된 KBP31705-Cl27, KBP30603-901을 기존 화합물인 cisplatin 및 carboplatin과 pharmacokinetic profile을 비교 검토하였다. 웅성 Sprague-Dawley rat을 sodium pentobarbital 마취하에서 방광 및 대퇴동맥과 정맥에 polyethylene tubing을 사용하여 catheterization시켰다. Urine 배출이 안정화되었을 때 대퇴정맥내로 cisplatin과 KBP31705-Cl27은 2 mg/kg, carboplatin과 KBP 30603-901은 20mg/kg 용량으로 주사한 후 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120 분에 대퇴동맥으로부터 혈액을 채취하였으며 urine은 약물투여 후 1시간 간격으로 4시간동안 채취하였다. Plasma와 urine중의 platinum농도는 inductively coupled plasma-mass spectrometer를 사용하여 측정하였고, pharmacokinetic parameters는 non-linear least square computer Program인 PCNONLIN을 이용하여 산출되었다. 혈중 platinum농도와 시간의 관계에서 KBP31705-Cl27은 cisplatin과 비교하여 alpha-phase에서 혈중 농도는 낮지만 비슷한 양상을 나타내었고, beta-phase에서는 비교적 느리게 소실됨을 보였다. Urine으로 4시간동안 배출된 platinum양은 각각 투여량의 52, 56%로서 두 약물에서 비슷하였다. 또한 KBP30603-901은 carboplatin과 비교하여 alpha-phase는 거의 비슷한 패턴을 나타내었으나, beta-phase는 훨씬 느리게 감소하여 반감기가 길다는 것을 보여 주었으며 또한 이것은 urine으로 4시간동안 배출된 platinum양이 KBP30603-901의 경우 투여량의 46%로서 carboplatin의 59%보다 적게 배출된다는 data와도 일관됨을 보여주었다. 이상의 결과로 볼 때 KBP30603-901이 다른 백금착물 항암제보다 체내에 머무르는 시간이 길어 혈중에서 보다 오랜 시간동안 머물러 높은 유효농도를 유지할 수 있을 것으로 사료된다.

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Clinical Investigation of Efficacy of Albumin Bound Paclitaxel plus Platinum Compounds as First-line Chemotherapy for Stage III/IV Squamous Non-small Cell Lung Cancer

  • Fang, Ying;Wang, Li;Xia, Guo-Hao;Shi, Mei-Qi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7453-7457
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    • 2014
  • Objective: To observe the efficacy and toxicity of nanoparticle albumin bound paclitaxel (nab-paclitaxel) plus platinum agent (cisplatin or carboplatin) as first line treatment for stage III/IV squamous non-small-cell lung cancer (NSCLC). Methods: Forty chemotherapy naive patients with stage III/IV squamous NSCLC received nab-paclitaxel $125mg/m^2$ on day 1 and day 8, cisplatin $75mg/m^2$ on day 1, carboplatin area under the concentration-time curve of 5 (AUC=5) on day 1. One cycle of treatment was 3 weeks, and at least two were completed in each case. Results: Of the 40 patients who participated in the study, 25 achieved partial responses (PR), 12 reached a stage of stable disease (SD), and 3 suffered progressive disease (PD). The overall response rate (ORR) was 62.5% and the disease control rate (DCR) was 92.5%. Of the 20 patients without surgery or radiotherapy, 10 achieved PR, 7 reached a stage of SD, and 3 PD. The ORR was 50.0% and the DCR was 85.0%. The median progression-free survival time (PFS) of patients without surgery or radiotherapy was 5.0 months. Of the 20 patients receiving surgery or radiotherapy, 15 had PR and 5 p had SD, with an ORR of 75.0% and a DCR of 85.0%. Specifically, the DDP arm demonstrated a significantly higher ORR than the CBP arm (100%vs 54.5%, P<0.05). Common treatment related adverse events were myelosuppression, gastrointestinal response, baldness and neurotoxicity, most of which were grade 1 to 2. Conclusion: Nab-paclitaxel plus platinum agent (cisplatin or carboplatin) is effective as a first-line chemotheraphy for stage III/IV squamous NSCLC, and its adverse effects are tolerable.

제3세대 백금착체 항암제 신약개발 1. Design, synthesis and antitumor activity of 3rd generation platinum complexes.

  • 김대기;김강혁;김종식;주상섭;김기협;김노경
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.73-73
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    • 1993
  • As part of a research program to develope 3rd generation anti tumor platinum complexes, a series of platinum complexes which have 4, 5-bis-(aminomethyl)- 1, 3-dioxolane derivatives as bidenate amine ligands, represented by the general structual formula was prepared. The R$_1$ and/or R$_2$ substituents in this series of platinum complexes can be hydrogen. alkyl, of jointly formed cyclohexane. Two Xs can be a bidenate leaving ligand such as 1, 1-cyclobutanedicarboxylate, malonate, dimethylmalonate, ethylmalonate, glycolate, L-lactate, or N-methyliminodiacetate. From based on the pharmacological and toxicological studies, we have chosen SKI 2053R, cis-malonato[(4R, 5R)-4, 5-bis(aminomethyl)-2-isopropyl-1, 3-dioxolane] platinum(II) complex (NSC D644591) as a candidate for clinical evaluation. The antitumor activity of a new anti tumor platinum complex, cis-malonato [(4R, 5R)-4, 5-bis(aminomethyl)-2-isopropyl-1, 3-dioxolane] platinum(II) (SKI 2053R, NSC D644591), was compared with those of cisplatin and carboplatin using murine tumors. We evaluated three platinum complexes against L1210/CPR, a subline of L1210 leukemia resistant to cisplatin for their abilities to overcome tumor resistance to cisplatin. The in vitro cytotoxicity of SKI 2053R to L1210 cell line was 2.5-fold less potent thann that of cisplatin, and was 10-fold more cytotoxic than that of carboplatin. SKI 2053R retained similar cytotoxic effect and anti tumor activity to L1210/CPR cell line, like the cytotoxicity of SKI 2053R to L1210 cell line, while either cisplatin or carboplatin had not property to overcome the acquired cisplatin-resistance. SKI 2053R exhibited greater or comparable antitumor activity than cisplatin or carboplatin in murine tumor models.

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Role of Concomitant Chemoradiation in Locally Advanced Head and Neck Cancers

  • Lasrado, Savita;Moras, Kuldeep;Pinto, George Jawahar Oliver;Bhat, Mahesh;Hegde, Sanath;Sathian, Brijesh;Luis, Neil Aaron
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.10
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    • pp.4147-4152
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    • 2014
  • Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion of treatment 65% of patients had complete response at the primary and regional sites, and 35% of patients had a partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at the primary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease. Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head and neck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary site conservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancers.

A Case of Syndrome of Inappropriate Secretion of Antidiuretic Hormone Following Chemotherapy in a Patient with Non-Small-Cell Lung Cancer (항암화학치료 후 발생한 항이뇨호르몬 부적절 분비 증후군 1예)

  • Lee, Kyoung Ju;Moon, Jae Young;Lee, Sung Yong;Lee, Sang Yeub;Kim, Je Hyeong;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.66 no.4
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    • pp.324-328
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    • 2009
  • The syndrome of inappropriate secretion of the antidiuretic hormone (SIADH) is a well recognized paraneoplastic phenomenon related to impaired water excretion, and can result in dilutional hyponatremia as well as central nervous system symptoms. It is characterized by a decrease in plasma osmolarity with inappropriately concentrated urine. The causes of SIADH are associated with pulmonary and endocrine disorders, central nervous system diseases, and malignancies, including lung cancer. The other causes of SIADH include some drugs, particularly chemotherapy agents. Anticancer drugs, such as cisplatin, vincristine, and cyclophosphamide are well known causes of SIADH but the mechanisms are unclear. Recently, we encountered a patient with advanced non-small cell lung cancer who suffered from general weakness and altered mentality after an intravenous carboplatin and gemcitabine combination.

Effect Of VPP/CAV Alternating Chemotherapy Versus Carboplatin/Etoposide(CE) Chemotherapy For Extensive Stage Small Cell Lung Cancer (전신병기(Extensive stage) 소세포 폐암 환자에서 항암 화학요법 성적 : VPP/CAV 및 Carboplatin/Etoposide(CE) 복합 화학요법의 치료효과)

  • Kim, Sun-Young;Suh, Jae-Chul;Kim, Myung-Hoon;Park, Hee-Sun;Kang, Dong-Won;Lee, Kyu-Seung;Ko, Dong-Seok;Kim, Geun-Hwa;Jeong, Seong-Su;Kim, Ju-Ock
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.5
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    • pp.740-747
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    • 2000
  • Background : To compare the efficacies and side effects of etoposide, cisplatin/cyclophosphamide, adriamycin, vincristine(VPP/CAV) with those of carboplatin etoposide(CE) in extensive stage small cell lung cancer patients. Method : Patients with extensive stage small lung cancer who has measurable disease were eligible. VPP/CAV group(n=22) was treated with cisplatin(60mg/$m^2$ iv. D1) etoposide(100mg/$m^2$ iv. D1-3), and 3 weeks later cyclophosphamide(1000mg/$m^2$ iv. D1), adriamycin( 40mg/$m^2$ iv. D1), and vincristine(1.4mg/$m^2$ iv. D1), were administered alternatively. CE group(n=22) was treated with carboplatin(325mg/$m^2$ iv. D1) and etoposide (100mg/$m^2$ iv. D1-3) ; repeated treatment was performed every 3 weeks. Result : Forty four patients were eligible for the study. The overall response rate was 61.4% (complete remission rate 0%, partial response rate 61.4%, stable disease rate 25%, progressive disease rate 13.6%), and median survival was 10.8 months. In VPP/CAV group, response rate was 54.5% (complete remission rate 0%, partial response rate 54.4%, stable disease rate 27.3%, progressive disease rate 18.2%), and, in carboplatin/etoposide group, the response rate was 68.2%(complete remission rate 0%, partial response rate 68.2%, stable disease rate 22.7%, progressive disease rate 9.1%). The median survival time was 9.5 months in the VPP/CAV group and 11 months in CE group. The toxicity of both group was moderate, and anemia was more frequent in the CE group. Conclusion : VPP/CAV regimen and CE regimen produced similar response rates and survival times in extensive stage small cell lung cancer patients. CE regimen may be effective as part of the initial therapy for extensive stage small cell lung cancer.

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Development of the 3rd Generation Anticancer Platinum Complex as New Drug

  • Cho, Yong-Baik;Ph. D.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2002.07a
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    • pp.97-102
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    • 2002
  • Life Science Research Center of SK Chemicals has developed a 3rd-generation anticancer platinum drug for the first time in the nation′s 100-year-old pharmaceutical industry. The Korea Food and Drug Administration (KFDA) approved the sale of "Sunpla" (code name SKI 2053R, general name : Heptaplatin) on July 14, 1999 for the treatment of advance, metastatic gastric cancer. Cisplatin, the 1 st-generation anticancer drug, which was developed by Bristol-Myers of the United States in 1976, is one of the most potent anticancer drugs and is a major component of combination chemotherapy for a variety of human cancers. However its clinical usefulness has frequently been limited not only by undesirable side effects such as severe renal toxicity, nausea, vomiting, ototoxicity, and neurotoxicity but also by the development of resistance. Carboplatin, the 2nd-generation anticancer platinum drug, which was also developed by Bristol-Myers in 1986, has modified the problems of the renal and gastrointestinal toxicities of cisplatin. Carboplatin, however, has no enhanced therapeutic efficacy over cisplatin and does not possess the property to overcome cross-resistance to cisplatin.

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Effect of Carboplatin in Combination with Hyperthermia on Cell Death in Human Retinoblastoma Cell Lines

  • Park, H.J.;Park, S.R.;Park, E.K.;Chung, H.S.;H.E.Ahn;Y.H.Rhee;Ha, S.W.;Lim, B.U.
    • Proceedings of the Korean Biophysical Society Conference
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    • 2001.06a
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    • pp.60-60
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    • 2001
  • We have investigated the effect of environmental acidity on the induction of apoptosis caused by heat and carboplatin alone or combined. The degree of apoptosis after heating at 42.5$^{\circ}C$ for 1h in pH 6.6 medium was greater than that in pH 7.5 medium in WERI human retinobalstoma cells. When heated in the same pH medium, more apoptosis occurred in the WERI cells than in the Y79 human retinoblastoma cells.(omitted)

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Successful Combination Chemotherapy for Nasal Carcinoma in a Dog

  • Kim, Su-Gang;Cho, Seok-Ho;Kim, Keon;Park, Hee-Myung;Park, Sang-Ik;Kim, Tae-Jung;Lee, Chang-Min
    • Journal of Veterinary Clinics
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    • v.36 no.5
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    • pp.274-277
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    • 2019
  • A Miniature Schnauzer presented with bilateral mucopurulent nasal discharge and sneezing. Computed tomography of the skull revealed exudates in the nasal cavity and frontal gyrus. Nasal swab cytology showed features of an epithelial-origin tumor. Histopathologic evaluation of the biopsy specimen revealed irregular proliferation of epithelial cells and necrotized tissue. Positive immunohistochemical staining confirmed the epithelial origin of the cells. The dog was diagnosed with nasal carcinoma and was treated with a chemotherapy protocol of carboplatin and piroxicam. This report confirms the effectiveness of combination chemotherapy only without radiotherapy in a dog with nasal carcinoma and provides a guideline for providing alternative treatment.