Oxaliplatin plus high-dose leucovorin and 5-fluorouracil (FOLFOX 4) in platinum-resistant and taxane-pretreated ovarian cancer: A phase II study

Pectasides, Dimitrios; Pectasides, Melina; Farmakis, Dimitrios; Gaglia, Asimina; Koumarianou, Anna; Nikolaou, Maria; Koumpou, Maria; Kountourakis, Panteleimon; Papaxoinis, George; Mitrou, Panagiota; Economopoulos, Theofanis; Raptis, Sotirios A.

doi:10.1016/j.ygyno.2004.06.029

Cited by 49 publications

(21 citation statements)

References 34 publications

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“…However, a recent combination chemotherapy with 5FU and oxaliplatin has brought about a remarkable improvement of the long-term survival rates of inoperable colorectal cancer patients (1). Consequently, this combination chemotherapy with 5FU and oxaliplatin has also been applied to recurrent ovarian cancer patients after standard chemotherapy with paclitaxel and carboplatin (2,3). Since 5FU-combination chemotherapies have been reapplied to various cancer patients in addition to colorectal cancer patients, 5FU-resistance may become a large clinical problem in future cancer chemotherapies.…”

Section: Introductionmentioning

confidence: 99%

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Establishment and characterization of monoclonal 5-fluorouracil-resistant cell lines derived from human endometrial adenocarcinoma

Tanaka

Bai²,

Toujima³

2010

Int J Oncol

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Abstract. To investigate acquired 5-fluorouracil (5FU)-resistance in cancer cells, we established four monoclonal 5FU-resistant cell lines from human endometrial adenocarcinoma cells by long-term 5FU-exposure cultures and limiting dilution cultures. The established subclones exhibited 5-25 times greater 5FU-resistance than the parent cells, and showed suppression of 5FU-induced DNA fragmentation. All four 5FU-resistant subclones were 25-125 times more resistant to SN38, 4-hydroxy-cyclophosphamide, paclitaxel and etoposide than the parent cells while none of the four subclones showed resistance to mitomycin. Two of the four subclones showed no resistance to pirarubicin and bleomycin. Although all four 5FU-resistant subclones were 5-25 times more resistant to anti-Fas IgM than the parent cells, the resistance levels to anti-Fas IgM of the individual subclones did not coincide with the strengths of their multidrug resistance. Karyotyping analyses revealed that the parent cells and the three 5FU-resistant subclones examined had normal 46XX karyotypes. These results indicate that the cell death signals induced by mitomycin, pirarubicin and bleomycin are distinctly different from the Fas-mediated apoptotic signals, that acquisition of 5FU-resistance can occur without any large chromosomal deletions or rearrangements, and that there are several possible molecular changes during the acquisition of 5FU-resistance. The established cell lines represent useful tools for investigating the mechanisms and treatments of acquired 5FU-resistance.

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Section: Introductionmentioning

confidence: 99%

“…Combination chemotherapy with 5FU and oxaliplatin was reported to be effective for recurrent ovarian cancer patients after TC therapy (2,3). Therefore, 5FU-resistance may become a large clinical problem for endometrial and ovarian cancer patients in the near future.…”

Section: Introductionmentioning

confidence: 99%

Establishment and characterization of monoclonal 5-fluorouracil-resistant cell lines derived from human endometrial adenocarcinoma

Tanaka

Bai²,

Toujima³

2010

Int J Oncol

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“…Four studies have demonstrated reasonable efficacy with an acceptable toxicity profile of FOLFOX (5FU/leucovorin + oxaliplatin) in platinum resistant, heavily pre-treated EOC [85][86][87][88] (Table 6). Again, these studies were all in the second-line or beyond setting and included only a handful of mEOC patients, so it is difficult to draw conclusions.…”

Section: Fu/leucovorin and Oxaliplatin (Folfox)mentioning

confidence: 99%

Mucinous ovarian cancer: A therapeutic review

Wen

Rush

Rickett

et al. 2016

Critical Reviews in Oncology/Hematology

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Highlights Mucinous epithelial ovarian cancer (mEOC) is a rare chemo-resistant subtype of ovarian cancer with distinct epidemiology, pathology and natural history.  mEOC can often masquerade as metastatic mucinous tumours from the gastrointestinal (GI) tract.  Molecularly, in contrast to high-grade serous ovarian cancer (HGSOC), mEOC are far less defined by p53 mutations and instead commonly harbour KRAS and HER 2 mutations.  The current gold standard of 1 st line platinum/taxane doublet chemotherapy, is more tailored towards HGSOC and generally ineffective for mEOC.  This review summarises the limited evidence for using GI style chemotherapeutic agents in treating mEOC and explores novel therapeutic possibilities such as targeting HER2, VEGF and Src. AbstractMucinous ovarian cancer represents approximately 3% of epithelial ovarian cancers (EOC).Despite this seemingly low prevalence, it remains a diagnostic and therapeutic conundrum that has resulted in numerous attempts to adopt novel strategies in managing this disease.Anecdotally, there has been a prevailing notion that established gold standard systemic regimens should be substituted for those utilised in cancers such as gastrointestinal (GI) malignancies; tumours that share more biological similarities than other EOC subtypes. This review summarises the plethora of small studies which have adopted this philosophy and influenced the design of the multinational GOG142 study, which was ultimately terminated due to poor accrual. To date, there is a paucity of evidence to support delivering 'GI style' chemotherapy for mucinous ovarian cancer over and above carboplatin-paclitaxel doublet therapy. Hence there is an urge to develop studies focused on targeted therapeutic agents driven by refined mutational analysis and conducted within the context of harmonised international collaborations.3

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“…5FU has often been administered to advanced gastric and colorectal cancer patients for more than 20 years, and a recent combination chemotherapy with 5FU and oxaliplatin has brought about a remarkable improvement in the long-term survival rates of inoperable colorectal cancer patients (22). Consequently, this combination chemotherapy with 5FU and oxaliplatin has also been applied to patients with recurrent ovarian cancer after standard chemotherapy with paclitaxel and carboplatin (23,24). Since 5FU combination chemotherapies have been reapplied to various cancer patients in addition to colorectal cancer patients, 5FU-resistance may become a large clinical problem in the current cancer chemotherapies.…”

Section: Introductionmentioning

confidence: 99%

Impaired death-associated protein kinase-mediated survival signals in 5-fluorouracil-resistant human endometrial adenocarcinoma cells

Tanaka¹,

Bai

Toujima

et al. 2012

Oncol Rep

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Abstract.A recent study showed that both 5-fluorouracil (5FU)-stimulated apoptosis and Fas-mediated apoptosis in human endometrial adenocarcinoma cells are enhanced by targeted knockdown of endogenous death-associated protein kinase (DAPK) with DAPK small-interfering RNAs. Therefore, we investigated the DAPK survival signals in three 5FU-resistant subclones. DAPK knockdown did not enhance 5FU-stimulated or Fas-mediated apoptosis in any of the three 5FU-resistant subclones, but the subclones acquired resistance to VP16-stimulated cell death that was DAPK-independent. Semiquantitative flow cytometric analyses showed that there was no differential expression in nine cell surface antigens, including Fas, and six intracellular molecules, including DAPK, that may regulate cell death or survival between the parent cells and 5FU-resistant cells. DAPK mRNA and protein were expressed in the 5FU-resistant subclones at similar levels to the parent cells. These results indicate that acquisition of 5FU-resistance may be accompanied by impairment of common apoptotic signals regulating both DAPK-dependent and DAPK-independent pathways. IntroductionThe death-associated protein kinase (DAPK) cDNA was isolated from human cervical carcinoma cells as a positive mediator of apoptosis triggered by interferon-γ (1). Recent investigations have revealed that DAPK functions as a Ca 2+ /calmodulin-dependent serine/threonine kinase to regulate cell death or survival (1-16). However, the physiological functions of DAPK have not been fully clarified. Loss of DAPK expression has been implicated in tumorigenesis and metastasis (3,4,13), suggesting a crucial role for DAPK in the apoptotic process under pathological conditions. On the other hand, inhibition of DAPK expression in HeLa cells, 3T3 fibroblasts, primary human vascular smooth muscle cells and various human uterine cancer cells using an antisense DAPK or small-interfering RNAs (siRNAs) for DAPK was found to increase apoptosis (6,12,15,16).Specific stimulation of Fas antigen can easily induce apoptotic cell death in differentiated human endometrial adenocarcinoma HHUA cells (17), and Fas-mediated apoptosis can be enhanced in a dose-dependent manner by targeted knockdown of endogenous DAPK protein expression by treatment with specific DAPK siRNAs (DAPK-KD) (18). Since DAPK-KD induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in HHUA cells (15), it is highly possible that DAPK-mediated signals constitutively suppress the tumor necrosis factor receptor-mediated cell death signaling common to the Fas-mediated and TRAIL-mediated pathways. Although typical apoptosis with DNA fragmentation can easily be induced in HHUA cells by treatment with 5-fluorouracil (5FU) (19), DAPK-KD increases apoptotic susceptibility to 5FU in HHUA cells (20). However, DAPK-KD has no effect on etoposide (VP16)-sensitivity in HHUA cells (20). Therefore, there are two apoptotic signals in HHUA cells, comprising DAPK-regulated and DAPK-independent death signals.In the human cervi...

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Oxaliplatin plus high-dose leucovorin and 5-fluorouracil (FOLFOX 4) in platinum-resistant and taxane-pretreated ovarian cancer: A phase II study

Cited by 49 publications

References 34 publications

Establishment and characterization of monoclonal 5-fluorouracil-resistant cell lines derived from human endometrial adenocarcinoma

Establishment and characterization of monoclonal 5-fluorouracil-resistant cell lines derived from human endometrial adenocarcinoma

Mucinous ovarian cancer: A therapeutic review

Impaired death-associated protein kinase-mediated survival signals in 5-fluorouracil-resistant human endometrial adenocarcinoma cells

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