Abstract
The taxanes' interaction with otheranticancer drugs have been extensivelyinvestigated in in vitro and inanimal models as well as in humans due tothe outstanding antitumor activity in abroad range of malignancies. Paclitaxel anddocetaxel are endowed of a rich and complexpharmacology whereby differentpharmacodynamic effects are observeddepending on the sequence of theiradministration in respect with thecompanion drug, and the type of drug thatis combined. Pharmacokinetic interferenceis often but not always a basis of thepharmacodynamic effect. In addition, thevehicle of clinical formulation, especiallyCremophor EL for paclitaxel, influence thepharmacological effect. Finally, newinteraction based on as yet unknownmechanisms drive the two taxanes tomultiple additive/synergistic relationshipswith new signal transduction drugs, such asmodulators of the epidermal-growth-factorfamily of receptors andfarnesyl-transferase inhibitors. Theongoing effort to better understanding sucha rich pharmacology is worth continuing inview of designing new and bettercombinations of the taxanes.
Similar content being viewed by others
References
Rowinsky EK: The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents. Annu Rev Med 48: 353–374, 1997
Rowinsky EK, Donehower RC: Paclitaxel (taxol) [published erratum appears in N Engl J Med 1995 Jul 6;333(1):75]. N Engl J Med 332: 1004–1014, 1995
Eisenhauer EA, Vermorken JB: The taxoids. Comparative clinical pharmacology and therapeutic potential. Drugs 55: 5–30, 1998
Belotti D, Vergani V, Drudis T, Borsotti P, Pitelli MR, Viale G, Giavazzi R, Taraboletti G: The microtubule-affecting drug paclitaxel has anti-angiogenic activity. Clin Cancer Res 2: 1843–1849, 1996
Rowinsky EK, Gilbert MR, McGuire WP, Noe DA, Grochow LB, Forastiere AA, Ettinger DS, Lubejko BG, Clark B, Sartorius SA: Sequences of taxol and cisplatin: a phase I and pharmacologic study. J Clin Oncol 9: 1691–1703, 1991
Gluck S, Sharan N, Chadderton T: In vitro combination of paclitaxel with five different cytotoxic drigs: effect on three different cell lines. Proc Am Ass Cancer Res 35: 335, 1994 (Abstract)
Capri G, Tarenzi E, Fulfaro F, Gianni L: The role of taxanes in the treatment of breast cancer. Semin Oncol 23: 68–75, 1996
Citardi M, Rowinsky EK, Schaefer KL: Sequence-dependent cytotoxicity between cisplatin and the antimicrotubule agents Taxol and Vincristine. Proc Am Ass Cancer Res 31: 2431, 1990 (Abstract)
Schellens JHM, Ma J, Bruno R, Paccaly D, Vergniol JC, Planting ASTh, de Boer-Dennert M, van der Burg MEL, Stoter G, Verweij J: Pharmacokinetics of cisplatin and Taxotere (docetaxel) and WBC DNA-adduct formation of cisplatin in the sequence Taxotere/cisplatin and cisplatin/ Taxotere in a phase II study in solid tumor patients. Proc Am Soc Clin Oncol 13: 132, 1994 (Abstract)
Nassim MA, Dulude H, Goel R: Interaction of paclitaxel and cisplatin in human lung carcinoma (HTB–56 cells). Proc Am Ass Cancer Res 40: 112, 1999 (Abstract)
Kelland LR, Abel G: Comparative in vitro cytotoxicity of taxol and Taxotere against cisplatin-sensitive and-resistant human ovarian carcinoma cell lines. Cancer Chemother Pharmacol 30: 444–450, 1992
Mc Keage MJ, Haddad GG, Ding L: Neuroprotective interactions between paclitaxel and cisplatin in female Wistar rats. Proc Am Ass Cancer Res 40: 561, 1999 (Abstract)
LeBlanc GA, Sundseth SS, Weber GF, Waxman DJ: Platinum anticancer drugs modulate P-450 mRNA levels and differentially alter hepatic drug and steroid hormone metabolism in male and female rats. Cancer Res 52: 540–547, 1992
Calvert AH, Newell DR, Gumbrell LA: Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol7: 1748–1756, 1989
Kearns CM, Belani CP, Erkmen K, Zuhowski M, Hiponia D, Zacharski D, Engstrom C, Ramanathan R, Trenn MR, Aisner J: Pharmacokinetics of paclitaxel and carboplatin in combination. Semin Oncol 22: 1–4; discuss, 1995
Shea T, Graham M, Bernard S, Steagall A, Wiley J, Serody J, Brecher M, Bentley S, Johnston C, Vaisman A: A clinical and pharmacokinetic study of high-dose carboplatin, paclitaxel, granulocyte colony-stimulating factor, and peripheral blood stem cells in patients with unresectable or metastatic cancer. Semin Oncol 22: 80–85, 1995
Schwartz GN, Pendyala L, Kindler H, Meropol N, Perez R, Raghavan D, Creaven P: The clinical development of paclitaxel and the paclitaxel/carboplatin combination. Eur J Cancer 34: 1543–1548, 1998
Creaven PJ, Raghavan D, Pendyala L, Loewen G, Kindler HL, Berghorn EJ, Jr.: Paclitaxel and carboplatin in early phase studies: Roswell Park Cancer Institute experience in the subset of patients with lung cancer. Semin Oncol 24: S12–13–S12–14, 1997
Calvert AH: A review of the pharmacokinetics and pharmacodynamics of combination carboplatin/paclitaxel. Semin Oncol 24: S2–85–S2–90, 1997
Huizing MT, van Warmerdam LJ, Rosing H, Schaefers MC, Lai A, Helmerhorst TJ, Veenhof CH, Birkhofer MJ, Rodenhuis S, Beijnen JH, ten Bokkel Huinink WW: Phase I and pharmacologic study of the combination paclitaxel and carboplatin as first-line chemotherapy in stage III and IV ovarian cancer. J Clin Oncol 15: 1953–1964, 1997
Huizing MT, Giaccone G, van Warmerdam LJ, Rosing H, Bakker PJ, Vermorken JB, Postmus PE, van Zandwijk N, Koolen MG, ten Bokkel Huinink WW, van der Vijgh WJ, Bierhorst FJ, Lai A, Dalesio O, Pinedo HM, Veenhof CH, Beijnen JH: Pharmacokinetics of paclitaxel and carboplatin in a dose-escalating and dose-sequencing study in patients with non-small-cell lung cancer. The European Cancer Centre. J Clin Oncol 15: 317–329, 1997
Kearns CM, Egorin MJ: Considerations regarding the lessthan-expected thrombocytopenia encountered with combination paclitaxel/carboplatin chemotherapy. Semin Oncol 24: S2–91–S2–96, 1997
Pluznik DH, Lee NS, Sawada T: Taxol induces the hematopoietic growth factor granulocyte-macrophage colonystimulating factor in murine B-cells by stabilization of granulocyte-macrophage colony-stimulating factor nuclear RNA. Cancer Res 54: 4150–4154, 1994
Shea TC: Mobilization of peripheral blood progenitor cells with paclitaxel-based chemotherapy. Semin Oncol 24: S2–105–S2–107, 1997
Raptis G, Tiersten A, Fennelly D: The addition of paclitaxel to high dose cyclophosphamide + filgrastim markedly enhances the mobilization of CD34+ peripheral blood progenitor cells in patients with responding metastatic breast cancer undergoing high dose chemotherapy. Proc ASCO 14: 313, 1995 (Abstract)
van Warmerdam LJ, Huizing MT, Giaccone G, Postmus PE, ten Bokkel Huinink WW, van Zandwijk N, Koolen MG, Helmerhorst TJ, van der Vijgh WJ, Veenhof CH, Beijnen JH: Clinical pharmacology of carboplatin administered in combination with paclitaxel. Semin Oncol 24: S2–97–S2–104, 1997
Selvaggi G, Belani CP: Carboplatin and paclitaxel in nonsmall cell lung cancer: the role of amifostine [In Process Citation]. Semin Oncol 26: 51–60, 1999
Engblom P, Rantanen V, Kulmala J, Helenius H, Grenman S: Additive and supra-additive cytotoxicity of cisplatin-taxane combinations in ovarian carcinoma cell lines. Br J Cancer 79: 286–292, 1999
Pronk LC, Schellens JH, Planting AS, van den Bent MJ, Hilkens P H, van der Burg ME, de Boer-Dennert M, Ma J, Blanc C, Harteveld M, Bruno R, Stoter G, Verweij J: Phase I and pharmacologic study of docetaxel and cisplatin in patients with advanced solid tumors. J Clin Oncol 15: 1071–1079, 1997
Ma J, Verweij J, Planting AS, Kolker HJ, Loos WJ, de Boer-Dennert M, van der Burg ME, Stoter G, Schellens JH: Docetaxel and paclitaxel inhibit DNA-adduct formation and intracellular accumulation of cisplatin in human leukocytes. Cancer Chemother Pharmacol 37: 382–384, 1996
de Graaff M, Maliepaard M, Pluim D, Floot BJ, Slaper-Cortenbach IC, Schellens JH: In vitro antagonistic cytotoxic interactions between platinum drugs and taxanes on bone marrow progenitor cell CFU-GM. Anticancer Drugs 10: 213–218, 1999
Greco FA, Erland JB, Morrissey LH, Burris HA, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD: Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin [In Process Citation]. Ann Oncol 11: 211–215, 2000
Mattson K, Saarinen A, Jekunen A: Combination treatment with docetaxel (Taxotere) and platinum compounds for nonsmall cell lung cancer. Semin Oncol 24: S14–5–S14–8, 1997
Mattson K, Vansteenkiste J, Stupp R, Bargetzi M, Saarinen A, Jekunen A, Fillet G, Teixeira M, Gatzemeier U, Olivares R, Soussan-Lazard K, Berille J: Phase II study of docetaxel alternating with cisplatin in chemotherapy-naive patients with advanced non-small cell lung cancer [In Process Citation]. Anticancer Drugs 11: 7–13, 2000
Liebmann JE, Fisher J, Teague D, Cook JA: Sequence dependence of paclitaxel (Taxol) combined with cisplatin or alkylators in human cancer cells. Oncol Res 6: 25–31, 1994
Kennedy MJ, Zahurak ML, Donehower RC, Noe DA, Sartorius S, Chen T L, Bowling K, Rowinsky EK: Phase I and pharmacologic study of sequences of paclitaxel and cyclophosphamide supported by granulocyte colony-stimulating factor in women with previously treated metastatic breast cancer. J Clin Oncol 14: 783–791, 1996
Bissery MC, Nohynek G, Sanderink GJ, Lavelle F: Docetaxel (Taxotere): a review of preclinical and clinical experience. Part I: Preclinical experience. Anticancer Drugs 6: 339–355, 363–368, 1995
Valero V: Combination docetaxel/cyclophosphamide in patients with advanced solid tumors. Oncology (Huntingt) 11: 34–36, 1997
Nabholtz JM, Smylie M, Mackey J R, Noel D, Paterson AH, al-Tweigeri T, Au D, Sansregret E, Delorme F, Riva A: Docetaxel/ doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. Oncology (Huntingt) 11: 37–41, 1997
Nabholtz JM, Mackey J, Smylie M, Tonkin K: Taxane-based three-drug combination in metastatic and adjuvant treatment of breast cancer. Semin Oncol 25: 27–31, 1998
Shin DM: Paclitaxel (Taxol)/ifosfamide-based chemotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Semin Oncol 27: 36–40, 2000
Pronk LC, Schrijvers D, Schellens JH, de Bruijn EA, Planting AS, Locci-Tonelli D, Groult V, Verweij J, van Oosterom AT: Docetaxel and ifosfamide in patients with advanced solid tumors: results of a phase I study. Semin Oncol 25: 23–28, 1998
Chou TC, Otter GN, Sirotnak FM: Combined effects of edatrexate with taxol and taxotere against breast cancer cell growth. Proc Am Ass Cancer Res 34: 300, 1993 (Abstract)
D'Andrea G, Fennelly D, Norton L, Baselga J, Gilewski T, Hudis C, Moynahan ME, Raptis G, Sklarin N, Surbone A, Theodoulou M, Templeton MA, Yao TJ, Seidman AD: Phase I study of escalating doses of edatrexate in combination with paclitaxel in patients with metastatic breast cancer. Clin Cancer Res 5: 275–279, 1999
Rigas JR, Kris MG,Miller VA, Pisters KM, Heelan RT, Grant SC, Fennelly DW, Chou TC, Sirotnak FM: Phase I study of the sequential administration of edatrexate and paclitaxel in patients with advanced solid tumors. Ann Oncol 10: 601–603, 1999
Grem JL, Nguyen D, Monahan BP, Kao V, Geoffroy FJ: Sequence-dependent antagonism between fluorouracil and paclitaxel in human breast cancer cells. Biochem Pharmacol 58: 477–486, 1999
Vredenburgh J, Fishman R, Coniglio D, Matters L, Elkordy M, Ross M, Hussein A, Rubin P, Gilbert C, Petros W, Peters WP: The addition of paclitaxel to continuous infusion 5-fluorouracil is an active regimen for metastatic breast cancer. Am J Clin Oncol 21: 543–547, 1998
Van Den Neste E, de Valeriola D, Kerger J, Bleiberg H, Kusenda Z, Brassinne C, Bartholomeus S, Selleslags J, Hennebert P, Wythouck H, Cazenave I, Lefresne-Soulas F, Piccart M: A phase I and pharmacokinetic study of docetaxel administered in combination with continuous intravenous infusion of 5-fluorouracil in patients with advanced solid tumors. Clin Cancer Res 6: 64–71, 2000
Sawada N, Ishikawa T, Fukase Y, Nishida M, Yoshikubo T, Ishitsuka H: Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res 4: 1013–1019, 1998
Ding AH, Porteu F, Sanchez E, Nathan CF: Shared actions of endotoxin and taxol on TNF receptors and TNF release. Science 248: 370–372, 1990
Eda H, Fujimoto K, Watanabe S, Ura M, Hino A, Tanaka Y, Wada K, Ishitsuka H: Cytokines induce thymidine phosphorylase expression in tumor cells and make them more susceptible to 5′-deoxy-5-fluorouridine. Cancer Chemother Pharmacol 32: 333–338, 1993
Villalona-Calero MA, Weiss GR, Burris HA, Kraynak M, Rodrigues G, Drengler RL, Eckhardt SG, Reigner B, Moczygemba J, Burger HU, Griffin T, Von Hoff DD, Rowinsky EK: Phase I and pharmacokinetic study of the oral fluoropyrimidine capecitabine in combination with paclitaxel in patients with advanced solid malignancies. J Clin Oncol 17: 1915–1925, 1999
Theodossiou C, Cook JA, Fisher J, Teague D, Liebmann JE, Russo A, Mitchell JB: Interaction of gemcitabine with paclitaxel and cisplatin in human tumor cell lines. Int J Oncol 12: 825–832, 1998
Colomer R, Llombart A, Lluch A, Ojeda B, Barnadas A, Caranana V, Fernandez Y, De Paz L, Guillem V, Alonso S: Paclitaxel/gemcitabine administered every two weeks in advanced breast cancer: preliminary results of a phase II trial. Semin Oncol 27: 20–24, 2000
Gennari A, Donati S, Danesi R, Fogli S, Orlandini C, Del Tacca M, Conte PF: The gemcitabine/epirubicin/paclitaxel combination in advanced breast cancer. Semin Oncol 27: 14–19, 2000
Mavroudis D, Malamos N, Alexopoulos A, Kourousis C, Agelaki S, Sarra E, Potamianou A, Kosmas C, Rigatos G, Giannakakis T, Kalbakis K, Apostolaki F, Vlachonicolis J, Kakolyris S, Samonis G, Georgoulias V: Salvage chemotherapy in anthracycline-pretreated metastatic breast cancer patients with docetaxel and gemcitabine: a multicenter phase II trial. Greek Breast Cancer Cooperative Group. Ann Oncol 10: 211–215, 1999
Adams DJ: Synergy of Navelbine-Taxol combination treatment in two human breast cancer cell lines. Proc Am Ass Cancer Res 35: 1944, 1994 (Abstract)
Knick VC, Eberwein DJ, Miller CG: Preclinical activity of Navelbine and Taxol drug combinations. Proc Am Ass Cancer Res 35: 1945, 1994 (Abstract)
Budman DR, Weiselberg L, O'Mara V, Buchbinder A, Lichtman SM, Donahue L, Adams LM: A phase I study of sequential vinorelbine followed by paclitaxel. Ann Oncol 10: 861–863, 1999
Ellis GK, Gralow JR, Pierce HI, Williams MA, Livingston RB: Infusional paclitaxel and weekly vinorelbine chemotherapy with concurrent filgrastim for metastatic breast cancer: high complete response rate in a phase I-II study of doxorubicin-treated patients. J Clin Oncol 17: 1407–1412, 1999
Romero Acuna L, Langhi M, Perez J, Romero Acuna J, Machiavelli M, Lacava J, Vallejo C, Romero A, Fasce H, Ortiz E, Grasso S, Amato S, Rodriguez R, Barbieri M, Leone B: Vinorelbine and paclitaxel as first-line chemotherapy in metastatic breast cancer. J Clin Oncol 17: 74–81, 1999
Culine S, Roch I, Pinguet F, Romieu G, Bressolle F: Combination paclitaxel and vinorelbine therapy: in vitro cytotoxic interactions and dose-escalation study in breast cancer patients previously exposed to anthracyclines. Int J Oncol 14: 999–1006, 1999
Aoe K, Kiura K, Ueoka H, Tabata M, Matsumura T, Chikamori M, Matsushita A, Kohara H, Harada M: Effect of docetaxel with cisplatin or vinorelbine on lung cancer cell lines. Anticancer Res 19: 291–299, 1999
Miller V: Docetaxel (Taxotere) in combination with vinorelbine in non-small cell lung cancer. Semin Oncol 26: 12–14, 1999
de Matteis A, Nuzzo F, Rossi E, Landi G, Perrone F: Intestinal side-effects of docetaxel/vinorelbine combination [letter]. Lancet 355: 1098–1099, 2000
Chou TC, Motzer RJ, Tong Y, Bosl GJ: Computerized quantitation of synergism and antagonism of Taxol, topotecan,and cisplatin against human teratocarcinoma cell growth: a rational approach to clinical protocol design. J Natl Cancer Inst 19: 1517, 1994
Klaassen U, Harstrick A, Schleucher N, Vanhoefer U, Schroder J, Wilke H, Seeber S: Activity-and schedule-dependent interactions of paclitaxel, etoposide and hydroperoxyifosfamide in cisplatin-sensitive and-refractory human ovarian carcinoma cell lines. Br J Cancer 74: 224–228, 1996
Hahn SM, Liebmann JE, Cook J, Fisher J, Goldspiel B, Venzon D, Mitchell JB, Kaufman D: Taxol in combination with doxorubicin or etoposide. Possible antagonism in vitro. Cancer 72: 2705–2711, 1993
Perez EA, Buckwalter CA: Sequence-dependent cytotoxicity of etoposide and paclitaxel in human breast and lung cancer cell lines. Cancer Chemother Pharmacol 41: 448–452, 1998
Kano Y, Akutsu M, Suzuki K, Mori K, Yazawa Y, Tsunoda S: Schedule-dependent interactions between paclitaxel and etoposide in human carcinoma cell lines in vitro. Cancer Chemother Pharmacol 44: 381–388, 1999
Perez EA, Buckwalter CA, Reid JP: Combinations of paclitaxel and etoposide in the treatment of lung cancer. Semin Oncol 23: 21–25, 1996
Koechli OR, Sevin BU, Perras JP, Chou TC, Angioli R, Steren A, Untch M, Averette HE: Characteristics of the combination paclitaxel plus doxorubicin in breast cancer cell lines analyzed with the ATP-cell viability assay. Breast Cancer Res Treat 28: 21–27, 1993
Holmes FA, Madden T, Newman RA, Valero V, Theriault RL, Fraschini G, Walters RS, Booser DJ, Buzdar AU, Willey J, Hortobagyi GN: Sequence-dependent alteration of doxorubicin pharmacokinetics by paclitaxel in a phase I study of paclitaxel and doxorubicin in patients with metastatic breast cancer. J Clin Oncol 14: 2713–2721, 1996
Solis Recendez MG, Bichat F, Barbault H: Drug interaction between Taxotere (TXT) and Adriamycine (ADR) in mice: tissue ADR incorporation according to the schedule of administration. Proc Am Ass Cancer Res 40: 558, 1999 (Abstract)
Bajorko P, Flamigni A, Volpi A: Carcinoma della mammella: valutazioni in vitro della attività citotossica dell'associazione farmacologica di Taxolo e Adriamicina. Tumori 80: 107, 1994 (Abstract)
Cividalli A, Cruciani G, Livdi E, Cordelli E, Eletti B, Tirindelli Danesi D: Greater antitumor efficacy of paclitaxel administered before epirubicin in a mouse mammary carcinoma. J Cancer Res Clin Oncol 124: 236–244, 1998
Gianni L, Vigano L, Locatelli A, Capri G, Giani A, Tarenzi E, Bonadonna G: Human pharmacokinetic characterization and in vitro study of the interaction between doxorubicin and paclitaxel in patients with breast cancer. J Clin Oncol 15: 1906–1915, 1997
Millward MJ, Webster LK, Rischin D, Stokes KH, Toner GC, Bishop JF, Olver IN, Linahan BM, Linsenmeyer ME, Woodcock DM: Phase I trial of cremophor EL with bolus doxorubicin [In Process Citation]. Clin Cancer Res 4: 2321–2329, 1998
Gianni L, Munzone E, Capri G, Fulfaro F, Tarenzi E, Villani F, Spreafico C, Laffranchi A, Caraceni A, Martini C: Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study [see comments]. J Clin Oncol 13: 2688–2699, 1995
Minotti G, Cairo G, Monti E: Role of iron in anthracycline cardiotoxicity: new tunes for an old song? [published erratum appears in FASEB J 1999 Mar; 13(3): 594]. FASEB J 13: 199–212, 1999
Licata S, Saponiero A, Mordente A, Minotti G: Doxorubicin metabolism and toxicity in human myocardium: role of cytoplasmic deglycosidation and carbonyl reduction. Chem Res Toxicol 13: 414–420, 2000
Bachur NR: Biochemical pharmacology of the anthracycline antibiotics. In: Sartorelli AC (ed) Cancer Chemotherapy. American Chemical Society, Washington, DC, 1976, pp 58–70
D'Incalci M, Schuller J, Colombo T, Zucchetti M, Riva A: Taxoids in combination with anthracyclines and other agents: pharmacokinetic considerations. Semin Oncol 25: 16–20, 1998
Nabholtz JM, North S, Smylie M, Mackey J, Au HJ, Au R, Morrish D, Salter E, Tonkin K: Docetaxel (Taxotere) in combination with anthracyclines in the treatment of breast cancer. Semin Oncol 27: 11–18, 2000
Gianni L, Dombernowsky P, Sledge G, Amadori G, Martin M, Baynes R, Arbuck S, Weil C, Tuck D, Messina M, Winograd B: Cardiac function following combination therapy with Taxol (T) and Doxorubicin (A) for advanced breast cancer (ABC). Proc Am Soc Clin Oncol 17: 115a, 1998 (Abstract)
Dombernowsky P, Gehl J, Boesgaard M, Paaske T, Jensen BV: Doxorubicin and paclitaxel, a highly active combination in the treatment of metastatic breast cancer. Semin Oncol 23: 23–27, 1996
Dombernowsky P, Boesgaard M, Andersen E, Jensen BV: Doxorubicin plus paclitaxel in advanced breast cancer. Semin Oncol 24: S17–15–S17–8, 1997
Conte PF, Baldini E, Gennari A, Michelotti A, Salvadori B, Tibaldi C, Danesi R, Innocenti F, Gentile A, Dell'Anna R, Biadi O, Mariani M, Del Tacca M: Dose-finding study and pharmacokinetics of epirubicin and paclitaxel over 3 hours: a regimen with high activity and low cardiotoxicity in advanced breast cancer. J Clin Oncol 15: 2510–2517, 1997
Gianni L, Vigano L, Locatelli A, Giani A, Capri G, Bertuzzi A, Grasselli G, Tarenzi E, Bonadonna G: Different interference of paclitaxel(PTX) on human pharmacokinetics of doxorubicin (DOX) and epirubicin (EPI). Proc ASCO 16: 224a, 1997 (Abstract)
Esposito M, Venturini M, Vannozzi MO, Tolino G, Lunardi G, Garrone O, Angiolini C, Viale M, Bergaglio M, Del Mastro L, Rosso R: Comparative effects of paclitaxel and docetaxel on the metabolism and pharmacokinetics of epirubicin in breast cancer patients. J Clin Oncol 17: 1132–1140, 1999
Ceruti M, Tagini V, Recalenda V, Arpicco S, Cattel L, Airoldi M, Bumma C: Docetaxel in combination with epirubicin in metastatic breast cancer: pharmacokinetic interactions. Farmaco 54: 733–739, 1999
Crommentuyn KM, Schellens JH, van den Berg JD, Beijnen JH: In vitro metabolism of anti-cancer drugs, methods and applications: paclitaxel, docetaxel, tamoxifen and ifosfamide [In Process Citation]. Cancer Treat Rev 24: 345–366, 1998
Monsarrat B, Royer I, Wright M, Cresteil T: Biotransformation of taxoids by human cytochromes P450: structure–activity relationship. Bull Cancer 84: 125–133, 1997
Royer I, Monsarrat B, Sonnier M, Wright M, Cresteil T: Metabolism of docetaxel by human cytochromes P450: interactions with paclitaxel and other neoplastic drugs. Cancer Res 56: 58–65, 1996
Sparreboom A, van Tellingen O, Nooijen WJ, Beijnen JH: Nonlinear pharmacokinetics of paclitaxel in mice results from the pharmaceutical vehicle Cremophor EL. Cancer Res 56: 2112–2115, 1996
Webster LK, Cosson EJ, Stokes KH, Millward MJ: Effect of the paclitaxel vehicle, Cremophor EL, on the pharmacokinetics of doxorubicin and doxorubicinol in mice. Br J Cancer 73: 522–524, 1996
Colombo T, Parisi I, Zucchetti M, Sessa C, Goldhirsch A, D'Incalci M: Pharmacokinetic interactions of paclitaxel, docetaxel and their vehicles with doxorubicin [see comments]. Ann Oncol 10: 391–395, 1999
Colombo T, Gonzalez Paz O, Zucchetti M, Maneo A, Sessa C, Goldhirsch A, D'Incalci M, Maneo MM: Paclitaxel induces significant changes in epidoxorubicin distribution in mice [published erratum appears in Ann Oncol 1997 Feb; 8(2): 207]. Ann Oncol 7: 801–805, 1996
Ellis AG, Crinis NA, Webster LK: Inhibition of etoposide elimination in the isolated perfused rat liver by Cremophor EL and Tween 80. Cancer Chemother Pharmacol 38: 81–87, 1996
Ellis AG, Webster LK: Inhibition of paclitaxel elimination in the isolated perfused rat liver by Cremophor EL. Cancer Chemother Pharmacol 43: 13–18, 1999
Schuurhuis GJ, Broxterman HJ, Pinedo HM, van Heijningen TH, van Kalken CK, Vermorken JB, Spoelstra EC, Lankelma J: The polyoxyethylene castor oil Cremophor EL modifies multidrug resistance. Br J Cancer 62: 591–594, 1990
Woodcock DM, Jefferson S, Linsenmeyer ME, Crowther PJ, Chojnowski GM, Williams B, Bertoncello I: Reversal of the multidrug resistance phenotype with cremophor EL, a common vehicle for water-insoluble vitamins and drugs. Cancer Res 50: 4199–4203, 1990
Webster L, Linsenmeyer M, Millward M: Measurement of Cremophor-El following Taxol: plasma levels sufficient to reverse drug exclusion mediated by the multidrug-resistant phenotype. J Natl Cancer Inst 85: 1685–1690, 1993
Sparreboom A, Verweij J, van der Burg ME, Loos WJ, Brouwer E, Vigano L, Locatelli A, de Vos AI, Nooter K, Stoter G, Gianni L: Disposition of Cremophor EL in humans limits the potential for modulation of the multidrug resistance phenotype in vivo. Clin Cancer Res 4: 1937–1942, 1998
Sparreboom A, van Asperen J, Mayer U, Schinkel AH, Smit JW, Meijer DK, Borst P, Nooijen W J, Beijnen JH, van Tellingen O: Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci USA 94: 2031–2035, 1997
Schinkel AH, Mayer U, Wagenaar E, Mol CA, van Deemter L, Smit JJ, van der Valk MA, Voordouw AC, Spits H, van Tellingen O, Zijlmans JM, Fibbe WE, Borst P: Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc Natl Acad Sci USA 94: 4028–4033, 1997
van Tellingen O, Huizing MT, Panday VR, Schellens JH, Nooijen WJ, Beijnen JH: Cremophor EL causes (pseudo-) non-linear pharmacokinetics of paclitaxel in patients. Br J Cancer 81: 330–335, 1999
Sparreboom A, van Zuylen L, Brouwer E, Loos WJ, de Bruijn P, Gelderblom H, Pillay M, Nooter K, Stoter G, Verweij J: Cremophor EL-mediated alteration of paclitaxel distribution in human blood: clinical pharmacokinetic implications. Cancer Res 59: 1454–1457, 1999
Gianni L, Kearns CM, Giani A, Capri G, Vigano L, Locatelli A, Bonadonna G, Egorin MJ: Nonlinear pharmacokinetics and metabolism of paclitaxel and its pharmacokinetic/pharmacodynamic relationships in humans. J Clin Oncol 13: 180–190, 1995
Ohtsu T, Sasaki Y, Tamura T, Miyata Y, Nakanomyo H, Nishiwaki Y, Saijo N: Clinical pharmacokinetics and pharmacodynamics of paclitaxel: a 3-hour infusion versus a 24-hour infusion. Clin Cancer Res 1: 599–606, 1995
Liebmann J, Cook JA, Fisher J, Teague D, Mitchell JB: In vitro studies of Taxol as a radiation sensitizer in human tumor cells. J Natl Cancer Inst 86: 441–446, 1994
Liebmann J, Cook JA, Fisher J, Teague D, Mitchell JB: Changes in radiation survival curve parameters in human tumor and rodent cells exposed to paclitaxel (Taxol). Int J Radiat Oncol Biol Phys 29: 559–564, 1994
Milas L, Milas MM, Mason KA: Combination of taxanes with radiation: preclinical studies. Semin Radiat Oncol 9: 12–26, 1999
Choy H, Rodriguez F, Wilcox B, Koester SK, Degen D: Radiation sensitizing effects of Taxotere (RP56976). Proc Am Ass Cancer Res 33: 500, 1992 (Abstract)
Mason KA, Kishi K, Hunter N, Buchmiller L, Akimoto T, Komaki R, Milas L: Effect of docetaxel on the therapeutic ratio of fractionated radiotherapy in vivo. Clin Cancer Res 5: 4191–4198, 1999
Tolcher AW, Cowan KH, Solomon D, Ognibene F, Goldspiel B, Chang R, Noone MH, Denicoff AM, Barnes CS, Gossard MR, Fetsch PA, Berg SL, Balis FM, Venzon DJ, O'shaughnessy JA: Phase I crossover study of paclitaxel with r-verapamil in patients with metastatic breast cancer. Clin Oncol 14: 1173–1184, 1996
Fisher GA, Bartlett NL, Lum BL: Phase I trial of Taxol(T) with high dose cyclosporine (CsA) as a modulator of miltidrug resistance (MDR). Proc ASCO 13: 369, 1994 (Abstract)
Meerum Terwogt JM, Beijnen JH, ten Bokkel Huinink WW, Rosing H, Schellens JH:Co-administration of cyclosporin enables oral therapy with paclitaxel [letter]. Lancet 352: 285, 1998
Meerum Terwogt JM, Malingre MM, Beijnen JH, ten Bokkel Huinink WW, Rosing H, Koopman FJ, van Tellingen O, Swart M, Schellens JH: Coadministration of oral cyclosporin A enables oral therapy with paclitaxel. Clin Cancer Res 5: 3379–3384, 1999
Au JL, Li D, Gan Y, Gao X, Johnson AL, Johnston J, Millenbaugh NJ, Jang SH, Kuh HJ, Chen CT, Wientjes MG: Pharmacodynamics of immediate and delayed effects of paclitaxel: role of slow apoptosis and intracellular drug retention. Cancer Res 58: 2141–2148, 1998
Haldar S, Chintapalli J, Croce CM: Taxol induces bcl-2 phosphorylation and death of prostate cancer cells. Cancer Res 56: 1253–1255, 1996
Donaldson KL, Goolsby GL, Kiener PA, Wahl AF: Activation of p34cdc2 coincident with taxol-induced apoptosis. Cell Growth Differ 5: 1041–1050, 1994
Wang LG, Liu XM, Kreis W: The effect of anti-microtubule agents on signal transduction pathways of apoptosis: a review. Cancer Chemother Pharmacol 44: 355–361, 1999
Li W, Fan J, Banerjee D: Overexpression of p21(waf1) decrease G2-M arrest and apoptosisninduced by paclitaxel in human sarcoma cells lacking both p53 and functional Rb protein. Mol Pharmacol 55: 1088–1093, 1999
Stewart ZA, Mays D, Pietenpol JA: Defective G1-S cell cycle checkpoint function sensitizes cells to microtubule inhibitorinduced apoptosis. Cancer Res 59: 3831–3837, 1999
King TC, Estalilla OC, Safran H: Role of p53 and p16 gene alterations in determining response to concurrent paclitaxel and radiation in solid tumor. Semin Radiat Oncol 9: 4–11, 1999
Blagosklonny MV, Robey R, Bates S, Fojo T: Pretreatment with DNA-damaging agents permits selective killing of checkpoint-deficient cells by microtubule-active drugs. J Clin Invest 105: 533–539, 2000
Nielsen LL, Lipari P, Dell J, Gurnani M, Hajian G: Adenovirus-mediated p53 gene therapy and paclitaxel have synergistic efficacy in models of human head and neck, ovarian, prostate, and breast cancer. Clin Cancer Res 4: 835–846, 1998
Baselga J, Norton L, Coplan K, Shalaby R, Mendelsohn J: Antitumor activity of paclitaxel in combination with anti-growth factor receptor monoclonal antibodies in breast cancer xenografts. Proc Am Ass Cancer Res 35: 380, 1994
Mendelsohn J, Fan Z: Epidermal growth factor receptor family and chemosensitization. J Natl Cancer Inst 89: 341–343, 1997
Baselga J, Norton L, Albanell J, Kim YM, Mendelsohn J: Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubi196 cin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res 58: 2825–2831, 1998
Pegram M, Hsu S, Lewis G, Pietras R, Beryt M, Sliwkowski M, Coombs D, Baly D, Kabbinavar F, Slamon D: Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene 18: 2241–2251, 1999
Ueno NT, Yu D, Hung M-C: Chemosensitization of HER-2/neu-overexpressing human breast cancer cells to paclitaxel (Taxol) by adenovirus type 5 E1A. Oncogene 15: 953–960, 1997
Gianni L, Capri G, Mezzelani A, Valagussa P, Greco M, Bertuzzi A, Grasselli G, Tarenzi E, Moliterni A, Pilotti S, Bonadonna G: Her2/Neu (HER2) amplification and response to doxorubicin/paclitaxel (AT) on women with metastatic breast cancer. Proc Am Soc Clin Oncol 16: 139, 1997 (Abstract)
Slamon D, Leyland-Jones B, Shak S: Addition of Herceptin (Humanized anti-HER2 antibody) to first line chemotherapy for HER2 overexpressing metastatic breast cancer (HER2+/MCB) markedly increases anticancer activity: a randomized, multinational, controlled Phase III trial. Proc ASCO 377, 1999 (Abstract)
Seidman AD, Fornier M, Esteva F, Tan L, Kaptain S, Bach A, Arroyo CD: Final Report: Weekly (W) Herceptin (H) and Taxol (T) for Metastatic Breast Cancer (MBC): Analysis of Efficacy by HER2 Immunophenotype[Immunohistochemistry (IHC)] and Gene Amplification[Fluorescent in-Situ Hybridization(FISH)]. Proc Am Soc Clin Oncol 19: 319, 2000 (Abstract)
Moasser MM, Sepp-Lorenzino L, Kohl NE, Oliff A, Balog A, Su DS, Danishefsky SJ, Rosen N: Farnesyl transferase inhibitors cause enhanced mitotic sensitivity to taxol and epothilones. Proc Natl Acad Sci USA 95: 1369–1374, 1998
Sepp-Lorenzino L, Ma Z, Rands E, Kohl NE, Gibbs JB, Oliff A, Rosen N: A peptidomimetic inhibitor of farnesyl: protein transferase blocks the anchorage-dependent and-independent growth of human tumor cell lines. Cancer Res 55: 5302–5309, 1995
Lebowitz PF, Davide JP, Prendergast GC: Evidence that farnesyltransferase inhibitors suppress Ras transformation by interfering with Rho activity. Mol Cell Biol 15: 6613–6622, 1995
Klauber N, Parangi S, Flynn E, Hamel E, D'Amato RJ: Inhibition of angiogenesis and breast cancer in mice by the microtubule inhibitors 2-methoxyestradiol and taxol. Cancer Res 57: 81–86, 1997
Schimming R, Hunter NR, Mason KA, Milas L: [Inhibition of tumor neo-angiogenesis and induction of apoptosis as properties of docetaxel (taxotere)]. Mund Kiefer Gesichtschir 3: 210–212, 1999
Griffon-Etienne G, Boucher Y, Brekken C, Suit HD, Jain RK: Taxane-induced apoptosis decompresses blood vessels and lowers interstitial fluid pressure in solid tumors: clinical implications. Cancer Res 59: 3776–3782, 1999
Evan G, Littlewood T: A matter of life and cell death. Science 281: 1317–1322, 1998
Li CJ, Li YZ, Pinto AV, Pardee AB: Potent inhibition of tumor survival in vivo by beta-lapachone plus taxol: combining drugs imposes different artificial checkpoints. Proc Natl Acad Sci USA 96: 13369–13374, 1999
Ciardiello F, Caputo R, Bianco R, Damiano V, Pomatico, De Placido S, Bianco AR, Tortora G: Potentation of cytotoxic drug activity in human cancer cells by ZD1839('IRESSA'), an EGFR-selective tyrosine kinase inhibitor. Proc Am Ass Cancer Res 3075, 2000 (Abstract)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vigano, L., Locatelli, A., Grasselli, G. et al. Drug Interactions of Paclitaxel and Docetaxel and their Relevance for the Design of Combination Therapy. Invest New Drugs 19, 179–196 (2001). https://doi.org/10.1023/A:1010691218625
Issue Date:
DOI: https://doi.org/10.1023/A:1010691218625