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Irinotecan as a Second-line Chemotherapy for Small Cell Lung Cancer: a Systemic Analysis

  • Zhang, Ming-Qian;Lin, Xin;Li, Yan;Lu, Shuang
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1993-1995
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    • 2015
  • Purpose: This analysis was conducted to evaluate the efficacy and safety of irinotecan based regimens as second-line chemotherapy in treating patients with small cell lung cancer. Methods: Clinical studies evaluating the efficacy and safety of irinotecan based regimens as second-line chemotherapy for patients with small cell lung cancer were identified using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In irinotecan based regimens as second-line chemotherapy, 4 clinical studies which including 155 patients with small cell lung cancer were considered eligible for inclusion. In all chemotherapy consisted of irinotecan with or without nedaplatin. Pooled analysis suggested that, in all patients, the pooled RR was 27.1% (42/155) in irinotecan based regimens. Nausea, vomiting, diarrhea and myelosuppression were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment related death occurred with the irinotecan based treatments. Conclusion: This systemic analysis suggests that irinotecan based regimens as second-line chemotherapy are associated with mild response rate and acceptable toxicity for patients with small cell lung cancer.

Formulation and Evaluation of Irinotecan Suppository for Rectal Administration

  • Feng, Haiyang;Zhu, Yuping;Li, Dechuan
    • Biomolecules & Therapeutics
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    • v.22 no.1
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    • pp.78-81
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    • 2014
  • Irinotecan suppository was prepared using the moulding method with a homogeneous blend. A sensitive and specific fluorescence method was developed and validated for the determination of irinotecan in plasma using HPLC. The pharmacokinetics of intravenous administered and rectal administered in rabbits was investigated. Following a single intravenous dose of irinotecan (50 mg/kg), the plasma irinotecan concentration demonstrated a bi-exponential decay, with a rapid decline over 15 min. $C_{max}$, $t_{1/2}$, $AUC_{0-30h}$ and $AUC_{0-{\infty}}$ were $16.1{\pm}2.7g/ml$, $7.6{\pm}1.2h$, $71.3{\pm}8.8{\mu}g{\cdot}h/ml$ and $82.3{\pm}9.5{\mu}g{\cdot}h/ml$, respectively. Following rectal administration of 100 mg/kg irinotecan, the plasma irinotecan concentration reached a peak of $5.3{\pm}2.5{\mu}g/ml$ at 4 h. The $AUC_{0-30h}$ and $AUC_{0-{\infty}}$ were $32.2{\pm}6.2{\mu}g{\cdot}h/ml$ and $41.6{\pm}7.2{\mu}g{\cdot}h/ml$, respectively. It representing ~50.6% of the absolute bioavailability.

Irinotecan as a Palliative Therapy for Metastatic Breast Cancer Patients after Previous Chemotherapy

  • Lan, Hai;Li, Yan;Lin, Cong-Yao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10745-10748
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    • 2015
  • Background: This analysis was conducted to evaluate the efficacy and safety of irinotecan based chemotherapy for treatment of patients with metastatic breast cancer (MBC) who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based. Methods: Clinical studies were identified using a predefined search strategy. Pooled response rates (RR) to treatment were calculated. Results: As irinotecan based regimens, 5 clinical studies which including 217 patients with refractory MBC were considered eligible for inclusion, with irinotecan, cisplatin, capecitabine, or TS-1. Systemic analysis suggested that, in all patients, pooled RR was 48.8% (106/217) with irinotecan based regimens. Thrombocytopenia and leukocytopenia were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment related deaths occurred. Conclusion: This systemic analysis suggests that irinotecan based regimens are beneficial and safe for treating patients with MBC after other chemotherapy.

Phase II Study of Induction Irinotecan + Cisplatin Chemotherapy Followed by Concurrent Irinotecan + Cisplatin Plus Twice-Daily Thoracic Radiotherapy (유제한성 병기의 소세포 폐암에서 3주 간격으로 시행된 irinotecan과 cisplatin을 이용한 과다분할 방사선 동시 요법)

  • Lee, Jeong Eun;Park, Hee Sun;Jung, Sung Soo;Kim, Ju Ock;Cho, Moon June;Kim, Jin Hwan;Lee, Choong Sik;Kim, Sun Young
    • Tuberculosis and Respiratory Diseases
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    • v.63 no.2
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    • pp.154-164
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    • 2007
  • Background: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. Methods: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan $60mg/m^2$ was administered intravenously on days 1 and 8 in combination with cisplatin $60mg/m^2$ on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. Results: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin $19.6mg/m^2$/week and irinotecan $38.2mg/m^2$/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. Conclusion: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.

Irinotecan Monotherapy Versus Irinotecan-Based Combination as Second-Line Chemotherapy in Advanced Gastric Cancer: A Meta-Analysis

  • Cho, Yo-Han;Yoon, So Young;Kim, Soo-Nyung
    • Cancer Research and Treatment
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    • v.49 no.1
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    • pp.255-262
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    • 2017
  • Purpose A meta-analysis was conducted to examine the question of whether combination regimens are more effective than monotherapy as a second-line chemotherapy in advanced gastric cancer. Materials and Methods The MEDLINE and the EMBASE databases and the Cochrane Central Register for Controlled Trials were searched using appropriate keywords. Only randomized controlled trials were eligible. Results Taxane-based study is rare; thus, four irinotecan-based studies were finally included in the meta-analysis. Out of 661 patients, 331 patients were assigned to combination therapy and 330 to monotherapy. Cisplatin or fluoropyrimidine (S-1 or 5-fluorouracil) was used as a combination partner to irinotecan. The pooled hazard ratio (HR) for overall survival (OS) and for progression-free survival (PFS) was 0.938 (95% confidence interval [CI], 0.796 to 1.104; p=0.442) and 0.815 (95% CI, 0.693 to 0.958; p=0.013). In subgroup analysis according to previous exposure to a partner agent, the PFS benefit of combination was observed only in the partially exposed group (HR, 0.784; 95% CI, 0.628 to 0.980; p=0.032). Conclusion Second-line irinotecan-based combination was not associated with increased OS, but with PFS benefit, which seemed particularly significant for patients receiving combination with a new agent.

Phase II Study of Irinotecan Plus Cisplatin as First Line therapy in Extensive Small-Cell Lung Cancer (확장기 소세포폐암에서 1차 치료로서 Irinotecan + Cisplatin 복합요법의 임상적 결과)

  • Hwang, Ki Eun;Kim, So Young;Jung, Jong Hoon;Park, Seong Hoon;Park, Jung Hyun;Kim, Hwi Jung;Kim, Hak Ryul;Yang, Sei Hoon;Jeong, Eun Taik
    • Tuberculosis and Respiratory Diseases
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    • v.61 no.2
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    • pp.143-149
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    • 2006
  • Background: Irinotecan (topoisomerase I inhibitor) is effective as a monotherapy against small-cell lung cancer(SCLC). Cisplatin is also an important drug against SCLC. A phase II study of irinotecan combined with cisplatin was carried out to evaluate the efficacy and toxicity of this combined regimen as a first line treatment in patients with extensive SCLC. Methods: Thirty-nine patients with previously untreated extensive SCLC were enrolled in this study. Irinotecan $60mg/m^2$ was administered intravenously on days 1, 8 and 15, and in combination with cisplatin $60mg/m^2$ on day 1 and every 28 days thereafter. Four cycles of chemotherapy were given to the patients. Results: The overall response rate was 77% with a complete response (CR) rate of 8%. The median survival time, 1- and 2-year survival rate were 14.8 months, 60.9% and 27.6%, respectively. The median progression free survival time, 6-and 12-month progression free survival rate were 8.4 months, 75% and 18.8%, respectively. The WHO grade 3 or more toxicity encountered were leukopenia (23%), diarrhea (26%). Two patients changed their chemotherapeutic regimen and one patient died from severe diarrhea. Conclusion: The combination of irinotecan and cisplatin is effective as a first line therapy in extensive SCLC is effective, but has severe or fatal diarrhea as toxicity.

Phase II Trial of Irinotecan plus Cisplatin Combination as First Line Therapy for Patients with Small cell Lung Cancer (소세포폐암 환자에서 1차 항암 치료제로서 Irinotecan 과 Cisplatin 병합요법에 관한 2상 연구)

  • Jeong, Hye Cheol;Lee, Sang Yeub;Kim, Jung Ha;Ha, Eun Sil;Jung, Jin Yong;Lee, Kyung Ju;Lee, Seung Hyeun;Kim, Se Joong;Lee, Eun Joo;Hur, Gyu Young;Lee, Sung Yong;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.60 no.1
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    • pp.57-64
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    • 2006
  • Background : Recently, there have been several studies showing that irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against extensive disease(ED) small cell lung cancer (SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of irinotecan plus cisplatin as a 1st line therapy for both limited and extensive disease SCLC. Methods : The study was conducted between January 2002 and June 2004. Patients were treated with $60mg/m^2$ irinotecan on day 1, 8, 15 and $60mg/m^2$ cisplatin on day 1, every 4 weeks. During concurrent thoracic irradiation for limited disease (LD)-SCLC patients, dose of irinotecan was reduced to $40mg/m^2$. Prophylactic cranial irradiation was given to patients with complete remission (CR) after chemotherapy. Results : Median ages of LD- and ED- SCLC were 64 years and performance status (PS) was 0-2. In patients with LD-SCLC, the response rate after concurrent chemoradiotherapy was 85% (CR, 6; Partial response [PR], 11). The median survival was 20 months (95% CIs, 15.6 to 24.4) with 1-and 2-year survival rates of 85% and 35%, respectively. Median progression free survival (PFS) was 12 months (95% CIs, 6.2 to 18.1) with 1- year PFS of 36%. In ED-SCLC, the response rate was 83.4% (CR, 1; PR, 14). The median survival was 14.5 months (95% CIs, 8.8 to 20.1) with 1-year survival rates of 75%. Median PFS was 6.3 months (95% CIs, 5.6 to 7.1) with 1- year PFS of 20%. The major toxicities (grade 3 or 4) of this regimen included leukopenia, anemia, thrombocytopenia, nausea/vomiting, and diarrhea without life threatening complication. Conclusion : Our data shows that the combination of irinotecan plus cisplatin as a first line therapy is effective and tolerable in the treatment of both LD- and ED- SCLC.

A Case of Typhlitis Developed after Chemotherapy with Irinotecan and Cisplatin in a Patient with Small Cell Lung Carcinoma

  • Ji, Eun Hye;Kim, Young Min;Kim, Soo Jeong;Yeom, Soo Jeong;Ha, Sung Eun;Kang, Hyeon Hui;Kang, Ji Young;Lee, Sang Haak;Moon, Hwa Sik
    • Tuberculosis and Respiratory Diseases
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    • v.73 no.5
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    • pp.288-291
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    • 2012
  • Typhlitis is a necrotizing colitis that usually occurs in neutropenic patients and develops most often in patients with hematologic malignancies such as leukemia and lymphoma. Typhlitis may proceed to bowel perforation, peritonitis and sepsis, which requires immediate treatment. Irinotecan is a semisynthetic analogue of the natural alkaloid camptothecin which prevents DNA from unwinding by inhibition of topoisomerase I. It is mainly used in colon cancer and small cell lung carcinoma (SCLC), of which the most common adverse effects are gastrointestinal toxicities. To the best of our knowledge, no case of typhlitis after chemotherapy with a standard dose of irinotecan in a solid tumor has been reported in the literature. We, herein, report the first case of typhlitis developed after chemotherapy combining irinotecan and cisplatin in a patient with SCLC.

Second-Line Irinotecan after Cisplatin, Fluoropyrimidin and Docetaxel for Chemotherapy of Metastatic Gastric Cancer

  • Kucukzeybek, Yuksel;Dirican, Ahmet;Erten, Cigdem;Somali, Isil;Can, Alper;Demir, Lutfiye;Bayoglu, Ibrahim Vedat;Akyol, Murat;Medeni, Murat;Tarhan, Mustafa Oktay
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2771-2774
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    • 2012
  • Aim: Tumors of upper gastrointestinal tract are among the cancers that have a quite lethal course. Cytotoxic chemotherapy is the most efficient therapeutic modality for metastatic gastric cancer. In patients who do not respond to first-line treatment, the response rate to second-line therapies is generally low and the toxicity rates high. This study concerned the efficacy and the side effect profile of second-line therapy with irinotecan in the patients who were being followed-up with the diagnosis of metastatic gastric cancer in $\dot{I}$zmir, Turkey. Materials and Methods: We retrospectively evaluated the efficacy and toxicity in 31 patients with metastatic gastric adenocarcinoma who presented to the polyclinic of Medical Oncology of Izmir Ataturk Education and Research Hospital between May 2008 and July 2011. All received chemotherapy regimens containing cisplatin, fluoropyrimidine (5-FU) and docetaxel as the first-line therapy for late stage disease. Irinotecan as a single agent was given at a dose of 210 mg/$m^2$ on each 21 days. Irinotecan (180 mg/$m^2$ on day 1), 5-FU (500 mg/$m^2$ on days 1-2) and leucovorin (LV; 60 mg/$m^2$ on days 1-2) as a combined regimen were given over a 14 day period. Results: Median age was 54 (range, 31-70). Irinotecan was given as a combined regimen for median 6 cycles (range, 3-12) and as a single agent for median 3 cycles (range, 1-10). Metastases were detected in one site in six patients (19%), in two different sites in 17 patients (55%) and in three or more sites in eight patients (26%). Four patients (12.9%) showed partial response and six patients (19.3%) showed stable disease. Progression-free survival (PFS) was found to be 3.26 months (95% CI, 2.3-4.2). Median overall survival (OS) was found to be 8.76 months (95% CI, 4.5-12.9). The most commonly seen grade 3/4 side effect was neutropenia but the the therapy was generally well-tolerated. Conclusions: In this study, it was demonstrated that second-line therapy with irinotecan given following the first-line therapy with cisplatin, fluoropyrimidine (5-FU) and docetaxel was efficient and safe. Further studies are needed for confirmation.

A Case of Organizing Pneumonia Associated with FOLFIRI Chemotherapy

  • Lee, Yoon Jeong;Kim, Jun-Hyun;Kim, Sun Woong;Kang, Won Chan;Kim, Soo Jung;Kim, Ji Hye;Kim, Sun Jong
    • Tuberculosis and Respiratory Diseases
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    • v.77 no.6
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    • pp.262-265
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    • 2014
  • The combination chemotherapy of irinotecan with 5-fluorouracil and leucovorin (FOLFIRI regimen) was recently proven to be beneficial in patients with advanced colorectal cancer. Pulmonary toxicity is very rare in adverse effects of irinotecan. No case of organizing pneumonia (also known as bronchiolitis obliterans organizing pneumonia) associated with FOLFIRI chemotherapy has been reported. We experienced a case of a 62-year-old man who presented persistent dry cough and progressive dyspnea after receiving chemotherapy with FOLFIRI regimen. After surgical lung biopsy, the patient was diagnosed with FOLFIRI chemotherapy-induced organizing pneumonia which was successfully treated with steroid therapy.