FEC (5-fluorouracil, epidoxorubicin and cyclophosphamide) versus EM (epidoxorubicin and mitomycin-C) with or without lonidamine as first-line treatment for advanced breast cancer. A multicentric randomised study. Final results

Pacini, P; Rinaldini, M.; Algeri, R; Guarneri, Alessia; Tucci, Enrico; Barsanti, G.; Neri, B; Bastiani, P.; Marzano, S.; Fallai, C.

doi:10.1016/s0959-8049(00)00068-x

Cited by 35 publications

(21 citation statements)

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“…Our data show for the first time that a dietary intervention targeted on DHA is a feasible approach that has potential to substantially increase survival in metastatic breast cancer patients treated with chemotherapy. When compared with historical data, the ORR observed in our population was within the range (30% to 60%) of that which has been reported in frontline FEC 75 chemotherapy for breast cancer metastasis (FESG, 1991(FESG, , 2000Pavesi et al, 1995;Pacini et al, 2000;Capotorto et al, 2003;Bonneterre et al, 2004). In terms of survival, frontline FEC 75 chemotherapy in this setting has been found to induce a median TTP ranging from 6 to 13 months and a median OS ranging from 18 to 23 months, with one single study reporting 28 months (FESG, 1991(FESG, , 2000Pavesi et al, 1995;Pacini et al, 2000;Capotorto et al, 2003;Bonneterre et al, 2004).…”

Section: Discussionsupporting

confidence: 79%

“…When compared with historical data, the ORR observed in our population was within the range (30% to 60%) of that which has been reported in frontline FEC 75 chemotherapy for breast cancer metastasis (FESG, 1991(FESG, , 2000Pavesi et al, 1995;Pacini et al, 2000;Capotorto et al, 2003;Bonneterre et al, 2004). In terms of survival, frontline FEC 75 chemotherapy in this setting has been found to induce a median TTP ranging from 6 to 13 months and a median OS ranging from 18 to 23 months, with one single study reporting 28 months (FESG, 1991(FESG, , 2000Pavesi et al, 1995;Pacini et al, 2000;Capotorto et al, 2003;Bonneterre et al, 2004). Although the median TTP (6 months) and OS (22 months) in our study were within the frame of published data, it should be stressed that our patient population had a particularly poor prognosis, as 68% had liver metastases in addition to other sites of metastases.…”

Section: Discussionsupporting

confidence: 79%

“…It is worth stressing that the reported rates of haematological toxicity rely heavily on the frequency of blood count assessment. They could range from 7% to 84% for neutropaenia, 1% to 21% for anaemia or from 1% to 9% for thrombocytopaenia (Stewart et al, 1997;Blajman et al, 1999;FESG, 2000;Pacini et al, 2000;Bonneterre et al, 2004;Zielinski et al, 2005). A slightly lower toxicity of chemotherapy with respect to anaemia and thrombopaenia was even observed in the H-DHA group.…”

Section: Discussionmentioning

confidence: 89%

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Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial

et al. 2009

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BACKGROUND: Breast cancer becomes lethal when visceral metastases develop. At this stage, anti-cancer treatments aim at relieving symptoms and delaying death without resulting in additional toxicity. On the basis of their differential anti-oxidant defence level, tumour cells can be made more sensitive to chemotherapy than non-tumour cells when membrane lipids are enriched with docosahexaenoic acid (DHA), a peroxidisable and oxidative-stress-inducing lipid of marine origin. METHODS: This open-label single-arm phase II study evaluated the safety and efficacy (response rate), as primary end points, of the addition of 1.8 g DHA daily to an anthracycline-based chemotherapy (FEC) regimen in breast cancer patients (n ¼ 25) with rapidly progressing visceral metastases. The secondary end points were time to progression (TTP) and overall survival (OS). RESULTS: The objective response rate was 44%. With a mean follow-up time of 31 months (range 2 -96 months), the median TTP was 6 months. Median OS was 22 months and reached 34 months in the sub-population of patients (n ¼ 12) with the highest plasma DHA incorporation. The most common grade 3 or 4 toxicity was neutropaenia (80%). CONCLUSION: DHA during chemotherapy was devoid of adverse side effects and can improve the outcome of chemotherapy when highly incorporated. DHA has a potential to specifically chemosensitise tumours.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 89%

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Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial

et al. 2009

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“…An enhanced antioxidant capacity allows cancer cells to not a universal finding, and mitochondrial respiration impairment is not a fixed feature of cancer cells [41] . Although the glycolytic inhibitors targeting the Warburg effect have been investigated in various cancer types, the glycolytic inhibitors with the exception of 3-BP (a lactate analog) [18,19, , 3-BrOP (a 3-bromopyruvate derivative) [71][72][73][74] , and dichloroacetate (DCA) have demonstrated low efficacy in arresting tumor growth when used alone [99] ; these inhibitors include 2-deoxy-D-glucose (a glucose analog) [70,[100][101][102][103][104][105][106][107][108][109][110][111][112] , lonidamine (a derivative of indazole-3-carboxylic acid) [113][114][115][116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132] , methyl jasmonate on HK , 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one on PFK [162]…”

Section: Initiation Of Metastasismentioning

confidence: 99%

Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication

Lee¹

2015

WJBC

125

115

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Aerobic glycolysis, i.e. , the Warburg effect, may contribute to the aggressive phenotype of hepatocellular carcinoma. However, increasing evidence highlights the limitations of the Warburg effect, such as high mitochondrial respiration and low glycolysis rates in cancer cells. To explain such contradictory phenomena with regard to the Warburg effect, a metabolic interplay between glycolytic and oxidative cells was proposed, i.e. , the "reverse Warburg effect". Aerobic glycolysis may also occur in the stromal compartment that surrounds the tumor; thus, the stromal cells feed the cancer cells with lactate and this interaction prevents the creation of an acidic condition in the tumor microenvironment. This concept provides great heterogeneity in tumors, which makes the disease difficult to cure using a single agent. Understanding metabolic flexibility by lactate shuttles offers new perspectives to develop treatments that target the hypoxic tumor microenvironment and overcome the limitations of glycolytic inhibitors.

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“…MMC has also shown good efficacy in combination strategies for MBC; in a randomized phase III study in first-line MBC, epirubicin and MMC (EM) (± lonidamid) demonstrated at least equivalent efficacy, in terms of ORR, time to progression (TTP), OS, and tolerability compared with standard 5-FU/epirubicin/cyclophosphamide (FEC) [24]. Furthermore, in combination with 5-FU and leucovorin in pretreated patients with MBC, MMC achieved a response rate of 43%, with favorable tolerability [25].…”

mentioning

confidence: 99%

Combination of capecitabine and mitomycin C as first-line treatment in patients with metastatic breast cancer

Vrdoljak

Boban²,

Omrčen³

et al. 2011

neo

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Optimal first-line chemotherapy for metastatic breast cancer (MBC) is challenging, particularly in patients previously treated with (neo) adjuvant anthracyclines/taxanes. Based on preclinical synergy with mitomycin C (MMC) and capecitabine in human tumor xenografts, we conducted a phase II study of first-line capecitabine and MMC in MBC. Patients received 3-weekly chemotherapy comprising MMC 8 mg/m 2 day 1 and capecitabine 1000 mg/m 2 twice daily, days 1-14. Combination chemotherapy was administered for a maximum six cycles, single-agent capecitabine could be continued until progressive disease or unacceptable toxicity. Thirty patients were included, objective response rate was 65.5%. After a median follow-up of 18.5 months, median time to progression was 8.5 months and median overall survival was 29.8 months. The main adverse events were thrombocytopenia, pneumonitis and hemolytic uremic syndrome. Our data suggest that first-line capecitabine and MMC has good antitumor activity in MBC, but is associated with MMC-specific toxicity.

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FEC (5-fluorouracil, epidoxorubicin and cyclophosphamide) versus EM (epidoxorubicin and mitomycin-C) with or without lonidamine as first-line treatment for advanced breast cancer. A multicentric randomised study. Final results

Cited by 35 publications

References 20 publications

Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial

Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial

Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication

Combination of capecitabine and mitomycin C as first-line treatment in patients with metastatic breast cancer

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