Irinotecan combined with docetaxel in pre-treated metastatic breast cancer patients: a phase II study

Stathopoulos, Georgios; Tsavdaridis, D.; Malamos, Nikos; Rigatos, Sotiris K.; Kosmas, C.; Pergantas, N.; Stathopoulos, J.; Xynotroulas, John

doi:10.1007/s00280-005-1006-3

Cited by 18 publications

(13 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An additional 8 patients showed stable disease. In the study from Greece (Stathopoulos et al, 2005), 48 patients pre-treated with anthracycline-combined chemotherapy, 30 patients were also treated with paclitaxel and 2 with docetaxel, were enrolled. All patients had WHO performance status of 0-2.…”

Section: Discussionmentioning

confidence: 99%

“…Via steps of screening the title and reading the abstract, 5 studies were identified (Frasci et al, 2005;Stathopoulos et al, 2005;Moulder et al, 2008;Lee et al, 2013;Otsuka, et al, 2013). These studies had been carried out in China, Japan, Korea, Europe and the USA.…”

Section: Resultsmentioning

confidence: 99%

“…Grade 3 and 4 neutropenia was observed in 18 patients (37.5%); 14 (29.2%) patients developed anemia and three (6.3%) thrombocytopenia. Regarding non-haematologic toxicities, alopecia and fatigue were common; grade 3 diarrhea was observed in only one (2.1%) patient (Stathopoulos et al, 2005). However, an American study is associated with low response rate (Perez et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Three patients had grade 3 diarrhea, 3 patients had grade 3 asthenia, and 1 patient had grade 3 hand-foot syndrome (Lee et al, 2013). Further higher responses of irinotecan in treating breast cancer patients with previous chemotherapy were obtained from Italy and Greece (Frasci et al, 2005;Stathopoulos et al, 2005). In study first authored by Frasci, 50 patients (48 with metastatic and 2 with locally advanced disease) were enrolled to evaluate the feasibility and activity of combination treatment with docetaxel and irinotecan, combined with filgrastim support, in anthracycline-and paclitaxel-pretreated MBC patients.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

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

Lan¹,

Li²,

Lin³

2015

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

Lan¹,

Li²,

Lin³

2015

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…Currently, several studies are evaluating the efficacy of CPT-11 in the treatment of solid tumors (Conroy et al, 2005;Delord et al, 2005;Reardon et al, 2005;Stathopoulos et al, 2005). Metabolism of CPT-11 is complex with the involvement of several enzymatic reactions (Rivory, 2000;Slatter et al, 2000).…”

mentioning

confidence: 99%

Expression and Characterization of a Human Carboxylesterase 2 Splice Variant

Schiel

Green²,

Davis³

et al. 2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

(1-piperidino)-1-piperidino] carbonyloxycamptothecin or Irinotecan] is a carbamate prodrug that is activated in vivo by carboxylesterase (CES)-2 to SN-38 (7-ethyl-10-hydroxycamptothecin), a potent topoisomerase I inhibitor. There is high interindividual variation when CPT-11 is used in the treatment of colorectal cancer. Several splice variants of CES2 are reported in the expressed sequence tag database. Real-time polymerase chain reaction was used to determine the abundance of the CES2 and splice variant of human carboxylesterase 2 (CES2⌬ 458 -473 ) transcripts in 10 paired samples of human tumor and normal colon tissue. The results showed that the CES2⌬ 458 -473 transcript accounts for an average of 6% of total CES2 transcripts in colon tissue, and there is large interindividual variation in CES2 expression in both tumor and normal colon samples. The carboxylesterase activity of the colon samples was determined by 4-methylumbelliferyl acetate hydrolysis assays and nondenaturing polyacrylamide gel electrophoresis followed by activity staining. Significant, positive correlations were found between CES2 expression levels and both measures of carboxylesterase activity. We cloned and expressed the CES2⌬ 458 -473 protein in Sf9 insect cells. The purification profiles and preliminary characterization of the CES2⌬ 458 -473 protein indicated that the expressed protein is folded and glycosylated like CES2. However, in vitro assays show that the CES2⌬ 458 -473 protein lacks 4-methylumbelliferyl acetate and irinotecan hydrolase activities. In conclusion, we found that the CES2⌬ 458 -473 protein is an inactive splice variant of CES2 and that its transcript is spliced at a relatively constant rate in tumor and normal colon tissue.CPT-11 is a semisynthetic camptothecin derivative that is approved for the treatment of metastatic colorectal cancer. Currently, several studies are evaluating the efficacy of CPT-11 in the treatment of solid tumors (Conroy et al., 2005;Delord et al., 2005;Reardon et al., 2005;Stathopoulos et al., 2005). Metabolism of CPT-11 is complex with the involvement of several enzymatic reactions (Rivory, 2000;Slatter et al., 2000). CYP3A4-dependent oxidation of CPT-11 results in the formation of APC and NPC (Haaz et al., 1998;Sai et al., 2001); carboxylesterase-dependent hydrolysis of CPT-11 and NPC results in the formation of the active metabolite SN-38 (Humerickhouse et al., 2000;Khanna et al., 2000;Sanghani et al., 2004) and UGT1A1 glucuronidates SN-38 to form the inactive SN-38-glucuronide (Hanioka et al., 2001). The key step in the metabolism of CPT-11 is its activation by carboxylesterases. There are three known human carboxylesterases, CES1, CES2, and CES3. CES2 has 100-and 2000-fold greater catalytic efficiency for irinotecan hydrolysis than CES1 and CES3, respectively . Therefore, CES2, which is predominantly expressed in the liver, small intestines, and colon (Satoh et al., 2002), is the most important carboxylesterase for the activation of CPT-11. Clinical data, reported by Xu et al....

show abstract

Docetaxel and irinotecan in recurrent or metastatic head and neck cancer

Argiris

Buchanan

Brockstein³

et al. 2009

Cancer

View full text Add to dashboard Cite

BACKGROUND:Docetaxel and irinotecan have single‐agent antitumor activity in squamous cell carcinoma of the head and neck (SCCHN). The authors sought to evaluate their combination in the treatment of patients with recurrent or metastatic SCCHN.METHODS:Eligibility criteria included recurrent or metastatic SCCHN with measurable disease, good performance status, and adequate laboratory parameters. Patients received docetaxel 35 mg/m2 and irinotecan 60 mg/m2, intravenously, on Days 1 and 8, every 21 days, until disease progression. The authors assessed UGT1A1 genotype, vascular endothelial growth factor (VEGF) in serum, and cyclooxygenase‐2 and VEGF in baseline tumor tissue.RESULTS:Fifty‐two patients were analyzable: 20 chemotherapy naive (Group A) and 32 previously treated with 1 chemotherapy regimen (Group B); 73% of patients had distant metastasis, and 60% were paclitaxel‐exposed. In Group A, 3 (15%) patients achieved a partial response; in Group B, 1 (3%) patient achieved a partial response. Median progression‐free survival (PFS) and overall survival were 3.3 and 8.2 months in Group A and 1.9 and 5.0 months in Group B, respectively. Common serious toxicities were diarrhea, fatigue, and anorexia. Patients with high serum VEGF had a median PFS of 2.8 months versus 1.7 months for patients with low VEGF (P = .085).CONCLUSIONS:Docetaxel and irinotecan had acceptable toxicities, but efficacy results in unselected patients with recurrent or metastatic SCCHN did not suggest an advantage over docetaxel alone or platinum‐based regimens. Cancer 2009. © 2009 American Cancer Society.

show abstract

Irinotecan combined with docetaxel in pre-treated metastatic breast cancer patients: a phase II study

Abstract: The irinotecan-docetaxel combination produces quite a high response rate in pre-treated advanced breast cancer patients.

Cited by 18 publications

References 31 publications

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

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

Expression and Characterization of a Human Carboxylesterase 2 Splice Variant

Docetaxel and irinotecan in recurrent or metastatic head and neck cancer

Contact Info

Product

Resources

About