Phase II study of docetaxel and irinotecan combination chemotherapy in metastatic gastric carcinoma

Park, S R; Chun, June Young; Yu, Miao; Lee, J H; Ryu, Keun Won; Choi, Il Ju; Kim, C G; Lee, J S; Kim, Y W; Bae, Jaeman; Kim, H K

doi:10.1038/sj.bjc.6603133

Cited by 22 publications

(13 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A doublet regimen, docetaxel/CPT-11, has been investigated by several study groups, but the observed clinical benefi t is unlikely to be promising: the regimen had modest activity and was highly toxic. Park et al [61] evaluated the effi cacy and safety of a docetaxel/CPT-11 regimen (docetaxel 30 mg/m 2 and CPT-11 70 mg/m 2 on days 1 and 8 every 3 weeks) in chemo-naive patients with metastatic gastric cancer (48 enrolled and 46 assessable). This study achieved an ORR of 45.7% (95% CI, 31.3%-60.1%), median TTP of, 4.5 months (95% CI, 3.8-5.2 months), and median OS of 8.2 months (95% CI, 5.8-10.6 months).…”

Section: Combinations With Irinotecan (Cpt-11)mentioning

confidence: 99%

Docetaxel: its role in current and future treatments for advanced gastric cancer

Nishiyama

Wada

2009

Gastric Cancer

View full text Add to dashboard Cite

regimen are undetermined [1][2][3][4]. Both CF (cisplatin [CDDP]/5-fl uorouracil ) and ECF (epirubicin/ CDDP/5-FU) have been considered as reference regimens to date [5][6][7][8], but the median survival time (MST) of the regimens does not exceed 7-10 months.Recently, several active agents have been used in gastric cancer therapy: the taxanes, irinotecan (CPT-11), oxaliplatin, S-1, and capecitabine, and more recently, biological agents such as cetuximab and bevacizumab have been used [1][2][3][4][5][6][7][8]. Current studies have thus focused on "new-generation agents," and much effort has been directed towards the development of the best regimen in various treatment settings. A series of these trials have provided several regimens that could become a standard treatment: the regimens include docetaxel/CDDP/5-FU (DCF) and CDDP/S-1 for advanced and metastatic cancer, and S-1 monotherapy in the adjuvant setting [9][10][11]. The advent of these newgeneration agents offers hope for improving patient outcomes.Among the new-generation agents, docetaxel now appears to be one of the most extensively investigated [12]. Docetaxel has demonstrated promising activity in gastric cancer, both as monotherapy [13,14] and in combination with other agents [15][16][17]. To date, docetaxel combinations, especially the DCF regimen, seem to be pivotal [9,10], and further, a taxane has been suggested to be the best potential partner of new oral 5-FU analogues and prodrugs such as S-1 and capecitabine [16,17]. This review will focus on the taxane, docetaxel, as a key agent in gastric cancer chemotherapy. Docetaxel as a single agent Mechanisms of action and metabolismDocetaxel is a semisynthetic analogue of paclitaxel, an extract from the rare Pacifi c yew tree Taxus brevifolia [18]. The chemical structure of docetaxel differs from

show abstract

Section: Combinations With Irinotecan (Cpt-11)mentioning

confidence: 99%

Docetaxel: its role in current and future treatments for advanced gastric cancer

Nishiyama

Wada

2009

Gastric Cancer

View full text Add to dashboard Cite

show abstract

“…In addition, CPT-11 has been prescribed for the treatment of small cell lung (3), breast (4), central nervous system (5), cervical (6), esophageal (7), gastric (8), and pancreatic (9) cancers as well as non -Hodgkin's lymphoma (10). The parent compound, camptothecin, is derived from the bark of the Chinese tree Camptotheca acuminata.…”

mentioning

confidence: 99%

Novel Delivery of SN38 Markedly Inhibits Tumor Growth in Xenografts, Including a Camptothecin-11–Refractory Model

Sapra

Zhao

Mehlig

et al. 2008

Clinical Cancer Research

161

148

View full text Add to dashboard Cite

Purpose: Clinical development of SN38, the active metabolite of camptothecin-11 (CPT-11), has been hampered due to its poor solubility. We have developed a novel polymer-drug conjugate, EZN-2208, made by linking SN38 with a multiarm polyethylene glycol via a glycine linker. Experimental Design: The in vitro cytotoxicity of EZN-2208 was tested using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. The therapeutic efficacy of EZN-2208 was evaluated in various xenografts, including an in vivoŝ elected CPT-11^refractory model. Tumor and blood concentration of EZN-2208, CPT-11, and SN38 was determined by high-performance liquid chromatography.Results: In vitro, EZN-2208 was 10-to 245-fold more potent than CPT-11in a panel of human tumor cell lines. In xenograft models of MX-1 breast, MiaPaCa-2 pancreatic, or HT-29 colon carcinoma, treatment with either a single dose or multiple injections of EZN-2208 was more efficacious (and in some cases produced tumor eradication for >16 weeks) compared with CPT-11 at their respective maximum tolerated doses or corresponding dose levels (P < 0.01).Most interestingly, EZN-2208 showed marked antitumor activity in animals that developed resistance to an 8-day course of CPT-11 treatment, as well as outperformed CPT-11 as secondround therapy in mice initially sensitive to CPT-11. EZN-2208 had prolonged circulation in the blood compared with CPT-11, resulting in high tumor exposure. This resulted in higher and longer-lasting tumor exposure of free SN38 in mice given EZN-2208 compared with those given CPT-11. Conclusions: Preclinical data suggest that EZN-2208 may be a promising anticancer agent in a wide variety of clinical settings, including tumors refractory to CPT-11treatment.

show abstract

“…The authors concluded that the combination at the doses and schedule investigated did not show significant activity. Additionally, in another study of docetaxel at a dose of 30 mg/m 2 in combination with irinotecan (70 mg/m 2 ) on days 1 and 8 every 3 weeks, the response rate was 45.7% among 46 evaluable patients, but grade 3/4 neutropenia was noted in 57.4% of the patients and febrile/neutropenic infection in 19.1% [17].…”

Section: Discussionmentioning

confidence: 97%

Intensive weekly chemotherapy with docetaxel, epirubicin and carboplatin with G-CSF support in patients with advanced gastric cancer

et al. 2007

View full text Add to dashboard Cite

Chemotherapy is an established modality in the management of patients with advanced gastric cancer but the optimal regimen has not been defined yet. Platinum and the anthracyclines and more recently docetaxel have shown activity in this tumor. The primary objective of this phase II study was to assess the efficacy and safety of an intensified regimen of weekly docetaxel/epirubicin/carboplatin (DECb) with growth factor support in previously untreated patients with advanced gastric cancer. A total of 72 patients with measurable disease received docetaxel at a dose of 30 mg/m2, epirubicin at a dose of 30 mg/m2 and carboplatin to a target area under the curve (AUC) of 2, every week for 6 consecutive weeks followed by 2 weeks' rest, with filgrastim support. Analysis was performed on an intention to treat basis. The main toxicity was hematologic with grade 3/4 neutropenia occurring in 35% of the patients. Other grade 3/4 toxicities included anemia (7%), thrombocytopenia (14%) and leucopenia (26%). The relative dose intensity of docetaxel and epirubicin was 62%. The overall response rate was 21%, the median time to tumor progression was 4.1 months and the median survival 7.3 months. Intensified weekly treatment with DECb has modest activity in the treatment of advanced gastric cancer. Myelotoxicity limits adequate drug delivery.

show abstract

Phase II study of docetaxel and irinotecan combination chemotherapy in metastatic gastric carcinoma

Cited by 22 publications

References 18 publications

Docetaxel: its role in current and future treatments for advanced gastric cancer

Docetaxel: its role in current and future treatments for advanced gastric cancer

Novel Delivery of SN38 Markedly Inhibits Tumor Growth in Xenografts, Including a Camptothecin-11–Refractory Model

Intensive weekly chemotherapy with docetaxel, epirubicin and carboplatin with G-CSF support in patients with advanced gastric cancer

Contact Info

Product

Resources

About