• Title, Summary, Keyword: platinum chemotherapy

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Docetaxel as Second-line Monotherapy for Advanced Non-small Cell Lung Cancer (진행성 비소세포폐암의 이차항암화학요법으로서 Docetaxel 단독요법의 성적)

  • Kang, Hyun Mo;Lee, Jeong Eun;Jang, Pil Soon;Lee, Yun Sun;Kwon, Sun Jung;An, Jin Young;Jung, Sung Soo;Kim, Ju Ock;Kim, Sun Young
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.5
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    • pp.465-472
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    • 2005
  • Background : The survival benefit associated with first-line chemotherapy in lung cancer has led to the need for second-line chemotherapy, for which Docetaxel ($Taxotere^{(R)}$) has proven efficacy in both settings. This study evaluated the safety and efficacy of docetaxel in patients with non-small cell lung cancer who had failed first-line platinum-based chemotherapy. Methods : Thirty one patients with non-small-cell lung cancer, who had failed first-line platinum-based chemotherapy, between March 1999 and August 2003, were enrolled in this study. Patients received intravenous docetaxel, either $75mg/m^2$ or $100mg/m^2$, with routine premedication every three weeks. Results : Fourteen patients (45.2%) had a partial response. The median survival and progression-free survival times were 12.5 months (95% CI 7.3-17.6) and 3.0 months (95% CI 1.6-4.5), respectively. This study showed 2 factors gave different survival benefits; the age (< 60 years: 20.1 months vs. ${\geq}60years$: 6.6 months, p = 0.0105) and the histological type (adenocarcinoma: 25.6 months vs. others: 7.9 months, p=0.0055). The predominant toxicity was neutropenia, which occurred as WHO grade 3 or 4 in 38.7 % of patients. One treatment-related death was also reported. Non-hematological toxicity was minor and easily controlled. There were no significant statistical differences in the survival benefit and toxicity between the two doses. Conclusion : Docetaxel, as second-line monotherapy, was well tolerated and effective in patients with non-small-cell lung cancer who failed first-line platinum-based chemotherapy.

Outcomes with Single Agent LIPO-DOX in Platinum-Resistant Ovarian and Fallopian Tube Cancers and Primary Peritoneal Adenocarcinoma - Chiang Mai University Hospital Experience

  • Suprasert, Prapaporn;Manopunya, Manatsawee;Cheewakriangkrai, Chalong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1145-1148
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    • 2014
  • Background: Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 $mg/m^2$ every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

Impact of the Copper Transporter Protein 1 (CTR1) Polymorphism on Adverse Events among Advanced Non-Small Cell Lung Cancer Patients Treated with Carboplatin-Gemcitabine Regimen

  • Kumpiro, Siriluk;Sriuranpong, Virote;Areepium, Nutthada
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.9
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    • pp.4391-4394
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    • 2016
  • Background: Platinum-based regimens are effective treatments for advanced non-small cell lung cancer (NSCLC), but the five-year survival rate is still less than 20%. One possible factor appears to be resistance involving polymorphisms in the CTR1 gene which plays an importance role in accumulation of platinum in the cytoplasm. Purpose: To establish both prevalence of CTR1 polymorphism and its impact on treatment related toxicity in Thai advanced NSCLC patients. Materials and Methods: Thirty-two advanced NSCLC participants received carboplatin and gemcitabine during January to June 2016 at King Chulalongkorn Memorial Hospital (KCMH) were recruited for analysis of the CTR1 rs12686377 genotype. These participants were planning to be treated with platinum-based chemotherapy for at least two cycles. Results: Allele frequency of CTR1 polymorphism $G{\rightarrow}T$ was found to be 25%. The results showed that genetic polymorphism at CTR1 rs12686377 was associated with emesis side effects (P = 0.020) and neuropathic symptoms (P = 0.010). In addition, hematologic side effects in terms of anemia also tended to be related to this polymorphism. Conclusions: This is the first study suggesting that polymorphism at CTR1 rs12686377 may be associated with toxicity from platinum-based regimens. Therefore, it could be a factor to aid in treatment decision-making.

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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    • 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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Prognostic Significance of GSTP1, XRCC1 and XRCC3 Polymorphisms in Non-small Cell Lung Cancer Patients

  • Ke, Hong-Gang;Li, Jun;Shen, Yi;You, Qing-Sheng;Yan, Yu;Dong, Han-Xuan;Liu, Jun-Hua;Shen, Zhen-Ya
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4413-4416
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    • 2012
  • Aim: Individual differences in chemosensitivity and clinical outcome in non-small cell lung cancer (NSCLC) patients treatment with platinum-based chemotherapy may be due to genetic factors. Our study aimed to investigate the prognostic role of GSTP1, XRCC1 and XRCC3 in NSCLC patients treated with chemotherapy. Methods: A total of 460 cases were consecutively selected from The Affiliated Hospital of Nantong University between Jan. 2003 to Nov. 2006, and all were followed-up until Nov. 2011. Genotyping of GSTP1 Ile105Val, XRCC1 Arg194Trp, XRCC1 Arg399Gln and XRCC3 Thr241Met was conducted by duplex polymerase-chain-reaction with confronting-two-pair primer methods. Results: Patients with GSTP Val/Val exhibited a shorter survival time, and had a 1.89 fold greater risk of death than did those with the IIe/IIe genotype. For XRCC1 Arg194Trp, the variant genotype Trp/Trp was significantly associated with a decreased risk of death from NSCLC when compared with the Arg/Arg. Individuals carrying XRCC1 399Gln/Gln genotype had a longer survival time, with a lowered risk of death from NSCLC. Conclusion: This study indicated that GSTP1 Ile105Val, XRCC1 Arg194Trp and XRCC1Arg399Gln genes have a role in modifying the effect of platinum-based chemotherapy for NSCLC patients in a Chinese population. Our findings provide information for therapeutic decisions for individualized therapy in NSCLC cases.

Role of Neoadjuvant Chemotherapy in the Management of Advanced Ovarian Cancer

  • Zhao, Dan;Wu, Ling-Ying;Wang, Xiao-Bing;Li, Xiao-Guang
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2369-2373
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    • 2015
  • Objective: To analyze efficacy of neoadjuvant chemotherapy for advanced ovarian cancer. Materials and Methods: A total of 107 patients with advanced ovarian cancer undergoing cytoreductive surgery were divided into a neoadjuvant chemotherapy group (n=61) and a primary debulking group (n=46) and retrospectively analyzed. Platinum-based adjuvant chemotherapy was applied to both groups after cytoreductive surgery ande overall and progression-free survival times were calculated. Results: No significant difference was observed in duration of hospitalization ($20.8{\pm}6.1$ vs. $20.2{\pm}5.4$ days, p>0.05). The operation time of neoadjuvant chemotherapy group was shorter than the initial surgery group ($3.1{\pm}0.7$ vs. $3.4{\pm}0.8$ h, p<0.05). There were no significant differences in median overall survival time between neoadjuvant chemotherapy group and surgery group (42 vs. 55 months, p>0.05). Similarly, there was no difference in median progression-free survival between neoadjuvant chemotherapy group and surgery group (16 vs. 17 months, p>0.05). The surgical residual tumor size demonstrated no significant difference between initial surgery and neoadjuvant chemotherapy groups (p>0.05). Multivariate analysis showed that more than 3 cycles of regimen with neoadjuvant chemotherapy was associated with more resistance to chemotherapy compared with patients without receiving neoadjuvant chemotherapy (OR: 5.962, 95%CI: 1.184-30.030, p<0.05). Conclusions:Neoadjuvant chemotherapy can shorten the operation time. However, it does not improve survival rates of advanced ovarian cancer patients.

Reactive Oxygen Species Modulator 1 (Romo1) Predicts Poor Outcomes in Advanced Non-small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy

  • Lee, Seung Hyeun;Choi, Sue In;Lee, Ji Sung;Kim, Chul Hwan;Jung, Won Jai;Lee, Eun Joo;Min, Kyung Hoon;Hur, Gyu Young;Lee, Seung Heon;Lee, Sung Yong;Kim, Je Hyeong;Lee, Sang Yeub;Shin, Chol;Shim, Jae Jeong;Kang, Kyung Ho;In, Kwang Ho
    • Cancer Research and Treatment
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    • v.49 no.1
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    • pp.141-149
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    • 2017
  • Purpose Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Materials and Methods Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated. Results A total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p < 0.001), and the median overall survival (OS) of the high Romo1 group was also significantly shorter than that of the low Romo1 group (8.4 months vs. 15.5 months, p < 0.001). Results of multivariate analyses showed significant association of high Romo1 expression with both poor PFS (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.71 to 4.44) and poor OS (HR, 3.99; 95% CI, 2.36 to 6.74). Results of the subgroup analysis showed a similar association regardless of tumor histology. Romo1 expression showed no association with any clinical parameter including age, sex, smoking status, stage, differentiation, or tumor histology. Conclusion Romo1 overexpression was associated with poor response to treatment and shorter survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting.

Phase II Study of Pemetrexed as Second or Third Line Combined Chemotherapy in Patients with Colorectal Cancer

  • Wu, Xue-Yan;Huang, Xin-En;You, Shan-Xi;Lu, Yan-Yan;Cao, Jie;Liu, Jin;Xiang, Jin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.2019-2022
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    • 2013
  • Purpose: To investigate the safety and efficacy of pemetrexed combined with chemotherapy as second or third line in patients with stage IV colorectal cancer (CRC). Patients and Methods: This trial was conducted to evaluate the effectiveness and safety of pemetrexed given to patients with recurrent or metastatic colorectal carcinoma who previously received 5-FU-based chemotherapy. All patients were required to have a histological diagnosis of colorectal adenocarcinoma with measurable metastatic disease and prior chemotherapy. Patients received pemetrexed at a dose of 500 $mg/m^2$ by 10 minute infusion on day 1, repeated every 21 days. Doses were modified depending on nadir counts. Combined chemotherapy included Oxaliplatin, Irinotecan and cis-platinum. Results: Thirty patients were enrolled and twenty-nine were evaluable for response. One patient did not have repeat radiological testing to determine response because he went off study after only one cycle of treatment for economic reasons. For 29 evaluable patients, 1 partial response, 6 stable disease and 22 progressive disease were recorded. Response rate was 3.45% (1/29). All responses occurred in patients receiving a starting dose of pemetrexed 500 $mg/m^2$. Median time to progression for all eligible patients was 2.5 months. The most common toxicities experienced were mild to moderate fever, hepatic damage, myelosuppression, nausea, vomiting, constipation, abdominal pain, diarrhea, and skin rash. Conclusion: Pemetrexed at 500 $mg/m^2$ given every three weeks combined with chemotherapy is associated with moderate response and good tolerability in patients with stage IV CRC.

Clinical Effects of the Combination Chemotherapy of Heptaplatin and 5-Fluorouracil in Advanced Gastric Cancer (진행성 위암 환자에서 Heptaplatin과 5-Fluorouracil 복합요법의 임상효과)

  • Shin, Gashil;Oh, Jung Mi
    • Korean Journal of Clinical Pharmacy
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    • v.14 no.2
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    • pp.61-70
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    • 2004
  • Heptaplatin is a new platinum derivative with antitumor activity against gastric cancer. Preclinical studies showed that it is less toxic than other platinum analogues. The purpose of this study is to evaluate the efficacy and toxicity of the combination therapy of heptaplatin and 5-fluorouracil in Korean advanced gastric cancer patients. This study was investigated retrospectively. The patients group consisted of 65 advanced gastric cancer patients with no prior radiotherapy. All patients received heptaplatin $400\;mg/m^2$ by 2-3 hour infusion on Day 1 and 5-FU $1000\;mg/m^2by 12-24 hour continuous infusion for 5 days. After the first cycle, subsequent doses were adjusted according to the toxicity. Courses were repeated every 28 days. As results, objective response occurred in 16 patients $(24.6\%)$. Two were complete and 14 were partial response. Median progression free survival was 32 weeks with $29\%$ of patients progression free at 1 year. The most common hematologic toxicity was anemia. Grade 3 or 4 anemia was seen at $2.7\%$ of treatment cycles. Grade 3 or higher leucopenia was seen at $1.2\%$ of cycles. Grade 3 or 4 neutropenia and thrombocytopenia occurred at $6.1\%\;and\;1.5\%$ of cycles, respectively. The most common nonhematologic toxicity was proteinuria. Though no patients experienced grade 3 or 4 proteinuria, proteinuria was a considerable factor for this chemotherapy. Grade 3 or higher gastrointestinal toxicities were nausea and vomiting ($4.6\%$ of patients) and diarrhea ($1.5\%$ of patients). Grade 2 renal toxicity with elevation of serum creatinine was seen in $0.3\%$ of cycles, which is less than that of other platinum analogues. This study showed that combination therapy of heptaplatin and 5-FU have modest antitumor activity against advanced gastric cancer without severe renal toxicity.

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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.