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Anticancer oral therapy: Emerging related issues

  • Giuseppe Luigi Banna
    Correspondence
    Corresponding author. Tel.: +39 347 6371111; fax: +39 095 7436588.
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    Division of Medical Oncology, Vittorio Emanuele University Hospital, Via Plebiscito, 628, 95124 Catania, Italy
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    g Tel.: +39 0331 449161; fax: +39 0331 449161.
    Elena Collovà
    Footnotes
    g Tel.: +39 0331 449161; fax: +39 0331 449161.
    Affiliations
    Division of Medical Oncology, Hospital of Legnano, Via Candiani, 2, 20025 Legnano, Milano, Italy
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    h Tel.: +39 091 6806710; fax: +39 091 6806906.
    Vittorio Gebbia
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    h Tel.: +39 091 6806710; fax: +39 091 6806906.
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    Division of Medical Oncology, La Maddalena Clinic for Cancer, University of Palermo, Italy
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    i Tel.: +39 095 7435196; fax: +39 095 7436588.
    Helga Lipari
    Footnotes
    i Tel.: +39 095 7435196; fax: +39 095 7436588.
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    Division of Medical Oncology, Vittorio Emanuele University Hospital, Via Plebiscito, 628, 95124 Catania, Italy
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    i Tel.: +39 095 7435196; fax: +39 095 7436588.
    Pietro Giuffrida
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    i Tel.: +39 095 7435196; fax: +39 095 7436588.
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    Division of Medical Oncology, Vittorio Emanuele University Hospital, Via Plebiscito, 628, 95124 Catania, Italy
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    j Tel.: +39 095 7436635; fax: +39 095 7436635.
    Sebastiano Cavallaro
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    j Tel.: +39 095 7436635; fax: +39 095 7436635.
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    Unit of Functional Genomics, Vittorio Emanuele University Hospital, Via Plebiscito, 628, 95124 Catania, Italy
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    i Tel.: +39 095 7435196; fax: +39 095 7436588.
    Rosaria Condorelli
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    i Tel.: +39 095 7435196; fax: +39 095 7436588.
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    Division of Medical Oncology, Vittorio Emanuele University Hospital, Via Plebiscito, 628, 95124 Catania, Italy
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    k Tel.: +39 095 7436611; fax: +39 095 7436588.
    Calogero Buscarino
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    k Tel.: +39 095 7436611; fax: +39 095 7436588.
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    Division of Medical Oncology, Vittorio Emanuele University Hospital, Via Plebiscito, 628, 95124 Catania, Italy
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    l Tel.: +39 0931 582461; fax: +39 0931 582462.
    Paolo Tralongo
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    Division of Medical Oncology, Di Maria Hospital, Contrada Chiusa di Carlo, Avola, Siracusa, Italy
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    m Tel.: +39 0942 579322; fax: +39 0942 5793222.
    Francesco Ferraù
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    m Tel.: +39 0942 579322; fax: +39 0942 5793222.
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    Division of Medical Oncology, San Vincenzo Hospital, Contrada Sirina, 98039 Taormina, Italy
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  • Author Footnotes
    g Tel.: +39 0331 449161; fax: +39 0331 449161.
    h Tel.: +39 091 6806710; fax: +39 091 6806906.
    i Tel.: +39 095 7435196; fax: +39 095 7436588.
    j Tel.: +39 095 7436635; fax: +39 095 7436635.
    k Tel.: +39 095 7436611; fax: +39 095 7436588.
    l Tel.: +39 0931 582461; fax: +39 0931 582462.
    m Tel.: +39 0942 579322; fax: +39 0942 5793222.

      Abstract

      The use of oral anticancer drugs has shown a steady increase. Most patients prefer anticancer oral therapy to intravenous treatment primarily for the convenience of a home-based therapy, although they require that the efficacy of oral therapy must be equivalent and toxicity not superior than those expected with the intravenous treatment. A better patient compliance, drug tolerability, convenience and possible better efficacy for oral therapy as compared to intravenous emerge as the major reasons to use oral anticancer agents among oncologists. Inter- and intra-individual pharmacokinetic variations in the bioavailability of oral anticancer drugs may be more relevant than for intravenous agents. Compliance is particularly important for oral therapy because it determines the dose-intensity of the treatment and ultimately treatment efficacy and toxicity. Patient stands as the most important determinant of compliance. Possible measures for an active and safe administration of oral therapy include a careful preliminary medical evaluation and selection of patients based on possible barriers to an adequate compliance, pharmacologic issues, patient-focused education, an improvement of the accessibility to healthcare service, as well as the development of home-care nursing symptom-focused interventions. Current evidences show similar quality of life profile between oral and intravenous treatments, although anticancer oral therapy seems to be more convenient in terms of administration and reduced time lost for work or other activities. Regarding cost-effectiveness, current evidences are in favor of oral therapy, mainly due to reduced need of visits and/or day in hospital for the administration of the drug and/or the management of adverse events.

      Keywords

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      References

        • Ruddy K.
        • Mayer E.
        • Partridge A.
        Patient adherence and persistence with oral anticancer treatment.
        CA Cancer J Clin. 2009; 59: 56-66
        • Weingart S.N.
        • Brown E.
        • Bach P.B.
        • et al.
        NCCN task force report: oral chemotherapy.
        J Natl Compr Canc Netw. 2008; 6: S1-S14
        • Kuppens I.E.
        • Breedveld P.
        • Beijnen J.H.
        • Schellens J.H.
        Modulation of oral drug bioavailability: from preclinical mechanism to therapeutic application.
        Cancer Invest. 2005; 23: 443-464
        • Liu G.
        • Franssen E.
        • Fitch M.I.
        • Warner E.
        Patient preferences for oral versus intravenous palliative chemotherapy.
        J Clin Oncol. 1997; 15: 110-115
      1. Wojtacki J, Wiraszka R, Rolka-Stempniewicz G, et al. Breast cancer patients’ preferences for oral versus intravenous second-line anticancer therapy. Eur J Cancer 2006;159:abstr 381.

        • Paley M.
        • Love N.
        • Carlson R.
        • et al.
        Preferences for oral, parenteral antitumor therapy: a survey of 260 patients with metastatic breast cancer.
        Proc Am Soc Clin Oncol. 2005; 23: 619
        • Fallowfield L.
        • Atkins L.
        • Catt S.
        • et al.
        Patients’ preference for administration of endocrine treatments by injection or tablets: results from a study of women with breast cancer.
        Ann Oncol. 2006; 17: 205-210
        • Catania C.
        • Didier F.
        • Leon M.E.
        • et al.
        Perception that oral anticancer treatments are less efficacious: development of a questionnaire to assess the possible prejudices of patients with cancer.
        Breast Cancer Res Treat. 2005; 92: 265-272
        • Pfeiffer P.
        • Mortensen J.P.
        • Bjerregaard B.
        • et al.
        Patient preference for oral or intravenous chemotherapy: a randomised cross-over trial comparing capecitabine and Nordic fluorouracil/leucovorin in patients with colorectal cancer.
        Eur J Cancer. 2006; 42: 2738-2743
        • Twelves C.
        • Gollins S.
        • Grieve R.
        • Samuel L.
        A randomised cross-over trial comparing patient preference for oral capecitabine and 5-fluorouracil/leucovorin regimens in patients with advanced colorectal cancer.
        Ann Oncol. 2006; 17: 239-245
        • Hennig I.M.
        • Naik J.D.
        • Brown S.
        • et al.
        Severe sequence-specific toxicity when capecitabine is given after Fluorouracil and leucovorin.
        J Clin Oncol. 2008; 26: 3411-3417
        • O’Neill V.J.
        • Twelves C.J.
        Oral cancer treatment: developments in chemotherapy and beyond.
        Br J Cancer. 2002; 87: 933-937
      2. Decision Resources Survey. Oral chemotherapeutic agents: key success factors and reimbursement issues. A survey of US oncologists and HMO pharmacy directors. June 2005. Roche data on file, 2006.

        • Collovà E.
        • Banna G.
        • Fiorio E.
        • et al.
        Opininions about the use of oral chemotherapy (CT) for cancer patients: results of a survey conducted among Italian oncologists.
        Ann Oncol. 2009; 20: B51
        • Ishikawa T.
        • Utoh M.
        • Sawada N.
        • Nishida M.
        • Fukase Y.
        • Sekiguchi F.
        • et al.
        Tumor selective delivery of 5-fluorouracil by capecitabine, a new oral fluoropyrimidine carbamate, in human cancer xenografts.
        Biochem Pharmacol. 1998; 55: 1091-1097
        • Kelly H.
        • Goldberg R.M.
        Systemic therapy for metastatic colorectal cancer: current options, current evidence.
        J Clin Oncol. 2005; 23: 4553-4560
        • Tabata T.
        • Katoh M.
        • Tokudome S.
        • et al.
        Bioactivation of capecitabine in human liver: involvement of the cytosolic enzyme on 5′-deoxy-5-fluorocytidine formation.
        Drug Metab Dispos. 2004; 32: 762-767
        • Lush R.M.
        • McCune J.S.
        • Tetteh L.
        • et al.
        The absolute bioavailability of oral vinorelbine in patients with solid tumors.
        Cancer Chemother Pharmacol. 2005; 56: 578-584
        • Marty M.
        • Fumoleau P.
        • Adenis A.
        • et al.
        Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors.
        Ann Oncol. 2001; 12: 1643-1649
        • Herben V.M.
        • ten Bokkel Huinink W.W.
        • Beijnen J.H.
        Clinical pharmacokinetics of topotecan.
        Clin Pharmacokinet. 1996; 31: 85-102
        • Hande K.
        • Messenger M.
        • Wagner J.
        • Krozely M.
        • Kaul S.
        Inter- and intrapatient variability in etoposide kinetics with oral and intravenous drug administration.
        Clin Cancer Res. 1999; 5: 2742-2747
        • Toffoli G.
        • Corona G.
        • Sorio R.
        • et al.
        Population pharmacokinetics and pharmacodynamics of oral etoposide.
        Br J Clin Pharmacol. 2001; 52: 511-519
        • Kruijtzer C.M.
        • Beijnen J.H.
        • Rosing H.
        • et al.
        Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918.
        J Clin Oncol. 2002; 20: 2943-2950
        • Malingre M.M.
        • Beijnen J.H.
        • Rosing H.
        • et al.
        Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients.
        Br J Cancer. 2001; 84: 42-47
        • Maliepaard M.
        • van Gastelen M.A.
        • Tohgo A.
        • et al.
        Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918.
        Clin Cancer Res. 2001; 7: 935-941
        • Diasio R.B.
        • Harris B.E.
        Clinical pharmacology of 5-fluorouracil.
        Clin Pharmacokinet. 1989; 16: 215-237
        • Gamelin E.
        • Delva R.
        • Jacob J.
        • et al.
        Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer.
        J Clin Oncol. 2008; 26: 2099-2105
        • de Jonge M.E.
        • Huitema A.D.
        • Schellens J.H.
        • Rodenhuis S.
        • Beijnen J.H.
        Population pharmacokinetics of orally administered paclitaxel formulated in Cremophor EL.
        Br J Clin Pharmacol. 2005; 59: 325-334
        • Rowinsky E.K.
        • Lucas V.S.
        • Hsieh A.L.
        • et al.
        The effects of food and divided dosing on the bioavailability of oral vinorelbine.
        Cancer Chemother Pharmacol. 1996; 39: 9-16
        • Ratain M.J.
        • Cohen E.E.
        The value meal: how to save $1, 700 per month or more on lapatinib.
        J Clin Oncol. 2007; 25: 3397-3398
        • Singh B.N.
        • Malhotra B.K.
        Effects of food on the clinical pharmacokinetics of anticancer agents: underlying mechanisms and implications for oral chemotherapy.
        Clin Pharmacokinet. 2004; 43: 1127-1156
        • Li Z.
        • Vachharajani N.N.
        • Krishna R.
        On the assessment of effects of food on the pharmacokinetics of drugs in early development.
        Biopharm Drug Dispos. 2002; 23: 165-171
        • Ratain M.J.
        Dear doctor: we really are not sure what dose of capecitabine you should prescribe for your patient.
        J Clin Oncol. 2002; 20: 1434-1435
        • Damle B.
        • Ravandi F.
        • Kaul S.
        • et al.
        Effect of food on the oral bioavailability of UFT and leucovorin in cancer patients.
        Clin Cancer Res. 2001; 7: 517-523
        • Sharma S.
        Patient selection for oral chemotherapy.
        Oncology (Williston Park). 2001; 15: 33-35
        • Findlay M.
        • von Minckwitz G.
        • Wardley A.
        Effective oral chemotherapy for breast cancer: pillars of strength.
        Ann Oncol. 2008; 19: 212-222
        • Haller D.G.
        • Cassidy J.
        • Clarke S.J.
        • et al.
        Potential regional differences for the tolerability profiles of fluoropyrimidines.
        J Clin Oncol. 2008; 26: 2118-2123
        • Beijnen J.H.
        • Schellens J.H.
        Drug interactions in oncology.
        Lancet Oncol. 2004; 5: 489-496
        • Riechelmann R.P.
        • Del Giglio A.
        Drug interactions in oncology: how common are they?.
        Ann Oncol. 2009; 20: 1907-1912
        • Del Giglio A.
        • Miranda V.
        • Fede A.
        • et al.
        Adverse drug reactions, drug interactions as causes of hospital admission in oncology.
        J Clin Oncol. 2009; 27: e20656
        • Haddad A.
        • Davis M.
        • Lagman R.
        The pharmacological importance of cytochrome CYP3A4 in the palliation of symptoms: review and recommendations for avoiding adverse drug interactions.
        Support Care Cancer. 2007; 15: 251-257
        • Bernard S.A.
        • Bruera E.
        Drug interactions in palliative care.
        J Clin Oncol. 2000; 18: 1780-1799
        • Reardon D.A.
        • Egorin M.J.
        • Quinn J.A.
        • et al.
        Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.
        J Clin Oncol. 2005; 23: 9359-9368
        • Yung A.
        • Vredenburgh J.
        • Cloughesy T.
        • et al.
        Erlotinib HCL for glioblastoma multiforme in first relapse, a phase II trial.
        J Clin Oncol. 2004; 22: 1555
        • Cramer J.A.
        • Roy A.
        • Burrell A.
        • et al.
        Medication compliance and persistence: terminology and definitions.
        Value Health. 2008; 11: 44-47
        • Bonadonna G.
        • Valagussa P.
        • Moliterni A.
        • Zambetti M.
        • Brambilla C.
        Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up.
        N Engl J Med. 1995; 332: 901-906
      3. Thompson AM, Dewar J, Fahey T, et al. Association of poor adherence to prescribed tamoxifen with risk of death from breast cancer. In: Breast Cancer Symposium, San Francisco, CA, 2007:abstr130.

        • Muss H.B.
        • Berry D.A.
        • Cirrincione C.T.
        • et al.
        Adjuvant chemotherapy in older women with early-stage breast cancer.
        N Engl J Med. 2009; 360: 2055-2065
        • Joensuu H.
        • Kellokumpu-Lehtinen P.L.
        • Huovinen R.
        • et al.
        Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial.
        Lancet Oncol. 2009; 10: 1145-1151
        • Maughan T.
        • Adams R.
        • Smith C.
        • et al.
        6LBA Addition of cetuximab to oxaliplatin-based combination chemotherapy (CT) in patients with KRAS wild-type advanced colorectal cancer (ACRC): a randomised superiority trial (MRC COIN).
        Eur J Cancer. 2009; 7: 4
        • Cassidy J.
        Benefits and drawbacks of the use of oral fluoropyrimidines as single-agent therapy in advanced colorectal cancer.
        Clin Colorectal Cancer. 2005; 5: S47-S50
      4. Partridge AH, Archer LE, Kornblith AB, et al. CALGB 60104: adherence with adjuvant capecitabine among women age 65 and older with early stage breast cancer treated on CALGB 49907. J Clin Oncol 2008;26:abstr6542.

        • Partridge A.H.
        • Avorn J.
        • Wang P.S.
        • Winer E.P.
        Adherence to therapy with oral antineoplastic agents.
        J Natl Cancer Inst. 2002; 94: 652-661
        • Lebovits A.H.
        • Strain J.J.
        • Schleifer S.J.
        • Tanaka J.S.
        • Bhardwaj S.
        • Messe M.R.
        Patient noncompliance with self-administered chemotherapy.
        Cancer. 1990; 65: 17-22
        • Lee C.R.
        • Nicholson P.W.
        • Souhami R.L.
        • Deshmukh A.A.
        Patient compliance with oral chemotherapy as assessed by a novel electronic technique.
        J Clin Oncol. 1992; 10: 1007-1013
        • Bonneterre J.
        • Chevalier B.
        • Focan C.
        • Mauriac L.
        • Piccart M.
        Phase I and pharmacokinetic study of weekly oral therapy with vinorelbine in patients with advanced breast cancer (ABC).
        Ann Oncol. 2001; 12: 1683-1691
        • Depierre A.
        • Freyer G.
        • Jassem J.
        • et al.
        Oral vinorelbine: feasibility and safety profile.
        Ann Oncol. 2001; 12: 1677-1681
        • Barron T.I.
        • Connolly R.
        • Bennett K.
        • Feely J.
        • Kennedy M.J.
        Early discontinuation of tamoxifen: a lesson for oncologists.
        Cancer. 2007; 109: 832-839
        • Bickell N.A.
        • Weidmann J.
        • Fei K.
        • Lin J.J.
        • Leventhal H.
        Underuse of breast cancer adjuvant treatment: patient knowledge, beliefs, and medical mistrust.
        J Clin Oncol. 2009; 27: 5160-5167
        • Waterhouse D.M.
        • Calzone K.A.
        • Mele C.
        • Brenner D.E.
        Adherence to oral tamoxifen: a comparison of patient self-report, pill counts, and microelectronic monitoring.
        J Clin Oncol. 1993; 11: 1189-1197
        • Faithfull S.
        • Deery P.
        Implementation of capecitabine (Xeloda) into a cancer centre: UK experience.
        Eur J Oncol Nurs. 2004; 8: S54-62
        • Chau I.
        • Legge S.
        • Fumoleau P.
        The vital role of education and information in patients receiving capecitabine (Xeloda).
        Eur J Oncol Nurs. 2004; 8: S41-S53
        • Molassiotis A.
        • Brearley S.
        • Saunders M.
        • et al.
        Effectiveness of a home care nursing program in the symptom management of patients with colorectal and breast cancer receiving oral chemotherapy: a randomized, controlled trial.
        J Clin Oncol. 2009; 27: 6191-6198
        • Geyer C.E.
        • Forster J.
        • Lindquist D.
        • et al.
        Lapatinib plus capecitabine for HER2-positive advanced breast cancer.
        N Engl J Med. 2006; 355: 2733-2743
        • Colleoni M.
        • Orlando L.
        • Sanna G.
        • et al.
        Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects.
        Ann Oncol. 2006; 17: 232-238
        • Zaniboni A.
        • Bolognesi A.
        • Arnoldi E.
        • Tabiadon D.
        • Barni S.
        • Intini C.
        Oral idarubicin and cyclophosphamide for metastatic breast cancer in elderly patients.
        Anticancer Drugs. 1998; 9: 295-299
        • Barnadas A.
        • Mendiola C.
        • Casado A.
        • et al.
        Combination of oral idarubicin and prednimustine in advanced breast cancer: a phase II study.
        Eur J Cancer. 1997; 33: 312-315
        • Nole F.
        • Catania C.
        • Munzone E.
        • et al.
        Capecitabine/vinorelbine: an effective and well-tolerated regimen for women with pretreated advanced-stage breast cancer.
        Clin Breast Cancer. 2006; 6: 518-524
        • Tubiana-Mathieu N.
        • Bougnoux P.
        • Becquart D.
        • et al.
        All-oral combination of oral vinorelbine and capecitabine as first-line chemotherapy in HER2-negative metastatic breast cancer: an International Phase II Trial.
        Br J Cancer. 2009; 101: 232-237
      5. Lorusso V, Spada M, Giampaglia M, et al. Oral vinorelbine plus capecitabine (oral vincap) combination in patients with advanced breast cancer (ABC). A phase II study of the GOIM (Gruppo Oncologico dell’Italia Meridionale). Ann Oncol 2006;17(Suppl. 7):vii15-7.

        • Finek J.
        • Holubec Jr., L.
        • Svoboda T.
        • et al.
        A phase II trial of oral vinorelbine and capecitabine in anthracycline pretreated patients with metastatic breast cancer.
        Anticancer Res. 2009; 29: 667-670
        • Nole F.
        • Catania C.
        • Sanna G.
        • et al.
        Dose-finding and pharmacokinetic study of an all-oral combination regimen of oral vinorelbine and capecitabine for patients with metastatic breast cancer.
        Ann Oncol. 2006; 17: 322-329
        • Kellokumpu-Lehtinen P.L.
        • Sunela K.
        • Lehtinen I.
        • Joensuu H.
        • Sjostrom-Mattson J.
        A phase I study of an all-oral combination of vinorelbine/capecitabine in patients with metastatic breast cancer previously treated with anthracyclines and/or taxanes.
        Clin Breast Cancer. 2006; 7: 401-405
      6. Cameron DA, Afseth J, Murray E. Oral idarubicin and capecitabine: a dose finding study confirms this as a safe, effective 1st line therapy for older women with breast cancer. Breast Cancer Res Treat 2002;76:abstr 341.

        • Findlay M.
        • Sharples K.
        • Riley G.
        • et al.
        Capecitabine and oral cyclophosphamide: a novel oral treatment combination for advanced cancer.
        Asia-Pacific J Clin Oncol. 2007; 3: 99-105
        • Tong D.K.
        • Cheng C.W.
        • Ching Chan S.
        • Ngor Wong L.
        • Chow L.W.
        Phase II study of an ‘all-oral’ regimen of capecitabine, idarubicin and cyclophosphamide for metastatic breast cancer–safety, efficacy and quality of life.
        Oncology. 2005; 68: 520-525
        • Cassidy J.
        • Clarke S.
        • Diaz-Rubio E.
        • et al.
        Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer.
        J Clin Oncol. 2008; 26: 2006-2012
        • Tan E.H.
        • Rolski J.
        • Grodzki T.
        • et al.
        Global Lung Oncology Branch trial 3 (GLOB3): final results of a randomised multinational phase III study alternating oral and i.v. vinorelbine plus cisplatin versus docetaxel plus cisplatin as first-line treatment of advanced non-small-cell lung cancer.
        Ann Oncol. 2009; 20: 1249-1256
        • Payne S.A.
        A study of quality of life in cancer patients receiving palliative chemotherapy.
        Soc Sci Med. 1992; 35: 1505-1509
        • Conroy T.
        • Hebbar M.
        • Bennouna J.
        • et al.
        Quality-of-life findings from a randomised phase-III study of XELOX vs. FOLFOX-6 in metastatic colorectal cancer.
        Br J Cancer. 2010; 102: 59-67
        • Kopec J.A.
        • Yothers G.
        • Ganz P.A.
        • et al.
        Quality of life in operable colon cancer patients receiving oral compared with intravenous chemotherapy: results from National Surgical Adjuvant Breast and Bowel Project Trial C-06.
        J Clin Oncol. 2007; 25: 424-430
        • Twelves C.
        • Boyer M.
        • Findlay M.
        • et al.
        Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma.
        Eur J Cancer. 2001; 37: 597-604
        • Jansman F.G.
        • Postma M.J.
        • van Hartskamp D.
        • Willemse P.H.
        • Brouwers J.R.
        Cost-benefit analysis of capecitabine versus 5-fluorouracil/leucovorin in the treatment of colorectal cancer in the Netherlands.
        Clin Ther. 2004; 26: 579-589
        • Cassidy J.
        • Douillard J.Y.
        • Twelves C.
        • et al.
        Pharmacoeconomic analysis of adjuvant oral capecitabine vs. intravenous 5-FU/LV in Dukes’ C colon cancer: the X-ACT trial.
        Br J Cancer. 2006; 94: 1122-1129
        • Di Costanzo F.
        • Ravasio R.
        • Sobrero A.
        • et al.
        Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer: economic evaluation in an Italian NHS setting.
        Clin Drug Investig. 2008; 28: 645-655
        • Douillard J.Y.
        • Tilleul P.
        • Ychou M.
        • et al.
        Cost consequences of adjuvant capecitabine, Mayo Clinic and de Gramont regimens for stage III colon cancer in the French setting.
        Oncology. 2007; 72: 248-254
        • Shiroiwa T.
        • Fukuda T.
        • Tsutani K.
        Cost-effectiveness analysis of XELOX for metastatic colorectal cancer based on the NO16966 and NO16967 trials.
        Br J Cancer. 2009; 101: 12-18
      7. Silberman G, Gupta S, Berkowitz N, et al. Cost-effectiveness of capecitabine, continuous infusion 5-FU, gemcitabine and vinorelbine in the treatment of metastatic breast cancer. Proc Am Soc Clin Oncol 1999;18:abstr1629.

      8. Baran RW, Dupere W, Susan M, et al. Clinical and economic outcomes associated with metastatic breast cancer in managed care populations: capecitabine (Xeloda) versus comparison therapies. Proc Am Soc Clin Oncol 2002;21:abstr1942.

      9. James R, Blanco C, Farina C. Savings in staff time as a result of switching from de Gramont to oral capecitabine for patients with advanced colorectal cancer. Eur J Cancer 2003;1(Suppl. 5):Abstr 271.

        • Gebbia V.
        • Puozzo C.
        Oral versus intravenous vinorelbine: clinical safety profile.
        Expert Opin Drug Saf. 2005; 4: 915-928
        • Colomer R.
        • Alba E.
        • Gonzalez-Martin A.
        • et al.
        Treatment of cancer with oral drugs: a position statement by the Spanish Society of Medical Oncology (SEOM).
        Ann Oncol. 2010; 21: 195-198