Abstract
The current practice for the dose calculation of most anticancer agents is based on body surface area in m2, although lower interpatient variation in pharmacokinetic parameters has been reported with pharmacokinetically guided administration. As chemotherapeutic agents have a narrow therapeutic window, pharmacokinetically guided administration may lead to less toxicity and higher efficacy than administration on the basis of body surface area.
Pharmacokinetically guided administration, using parameters such as area under the plasma concentration-time curve (AUC), steady-state plasma drug concentration and drug exposure time above a certain plasma concentration, has been studied for many antineoplastic agents. Assessment of pharmacokinetic profiles allows the characterisation of relationships between pharmacokinetic parameters and efficacy and toxicity. AUC appears to be more closely correlated with pharmacodynamics than does the dose per unit of body surface area.
In particular, the AUC-guided administration of carboplatin has been extensively studied, based on the close relationship between the renal clearance of the drug and glomerular filtration rate. Several formulae and limited sampling models have been derived to predict the AUC of carboplatin. The relationship between AUC and pharmacodynamics has also been studied for other anticancer agents, for example fluorouracil, topotecan, etoposide, cisplatin and busulfan, but all less extensively than for carboplatin. The pharmacokinetically guided administration of these agents needs to be investigated further before the use of alternative administration formulae can become standard clinical practice.
Prospective studies of pharmacokinetically guided versus surface area-based administration should be performed to validate pharmacokinetic-pharmacodynamic relationships and to facilitate optimal dosage of anticancer agents in the clinic.
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References
Grochow LB. Individualized dosing of anticancer drugs and the role of therapeutic monitoring. In: Grochow LB, Ames MM, editors. A clinician’s guide to chemotherapy pharmacokinetics and pharmacodynamics. Baltimore: Williams & Wilkins, 1998: 3–16.
Gibaldi M. Revisiting some factors contributing to variability. Ann Pharmacother 1992; 26: 1002–7.
Canal P, Chatelut E, Guichard S. Practical treatment guide for dose individualisation in cancer chemotherapy. Drugs 1998; 56: 1019–38.
Powis G. Effect of human renal and hepatic disease on the pharmacokinetics of anticancer drugs. Cancer Treat Rev 1982; 9: 85–124.
Gurney H. Dose calculation of anticancer drugs: a review of the current practice and introduction of an alternative. J Clin Oncol 1996; 14: 2590–611.
Donelli MG; Zucchetti M, Munzone E, et al. Pharmacokinetics of anticancer agents in patients with impaired liver function. Eur J Cancer 1997; 34: 33–46.
Kintzel PE, Dorr RT. Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function. Cancer Treat Rev 1995; 21: 33–64.
Ratain MJ, Schilsky RL, Conley BA, et al. Pharmacodynamics in cancer therapy. J Clin Oncol 1990; 8: 1739–53.
Workman P, Graham MA. Pharmacokinetics and chemotherapy. Eur J Cancer 1994; 30A: 706–10.
Judson IR. Pharmacokinetic modelling: a prelude to therapeutic drug monitoring for all cancer patients? Eur J Cancer 1995; 31A: 1733–5.
Desoize B, Robert J. Individual dose adaptation of anticancer drugs. Eur J Cancer 1994; 30A: 844–51.
Kobayashi K, Jodrell DI, Ratain MJ. Pharmacodynamic-pharmacokinetic relationships and therapeutic drug monitoring. In: Workman P, Graham MA, editors. Pharmacokinetics and cancer chemotherapy. Cold Spring Harbor: Cold Spring Harbor Laboratory Press, 1993: 51–87.
Egorin MJ. Overview of recent topics in clinical pharmacology of anticancer agents. Cancer Chemother Pharmacol 1998; 42 Suppl.: S22–30.
Evans WE, Relling MV, Rodman JH, et al. Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia. N Engl J Med 1998; 338: 499–505.
Evans WE, Crom WR, Abromowitch M, et al. Clinical pharmacodynamics of high-dose methotrexate in acute lymphocytic leukaemia. N Engl J Med 1986; 314: 471–7.
Fety R, Rolland F, Barberi-Heyob M, et al. Clinical impact of pharmacokinetically-guided dose adaptation of 5-fluorouracil: results from a multicentric randomized trial in patients with locally advanced head and neck carcinomas. Clin Cancer Res 1998; 4: 2039–45.
Ratain MJ, Schilsky RL, Choi KE, et al. Adaptive control of etoposide dosing: impact of interpatient pharmacodynamic variability. Clin Pharmacol Ther 1989; 45: 226–33.
Ratain MJ, Mick R, Schilsky RL, et al. Pharmacologically based dosing of etoposide: a means of safely increasing dose intensity. J Clin Oncol 1991; 9: 1480–6.
Sörensen BT, Strömgren A, Jakobsen P, et al. Renal handling of carboplatin. Cancer Chemother Pharmacol 1992; 30: 317–20.
Sörensen BT, Strömgren A, Jakobsen P, et al. Dose-toxicity relationship of carboplatin in combination with cyclophosphamide in ovarian cancer patients. Cancer Chemother Pharmacol 1991; 28 (5): 397–401.
van der Vijgh WJF. Clinical pharmacokinetics of carboplatin. Clin Pharmacokinet 1991; 21: 242–61.
Egorin MJ, Van Echo DA, Tipping SJ, et al. Pharmacokinetics and dosage reduction of cis-diammine (1,1-cyclobutane-dicarboxylato) platinum in patients with impaired renal function. Cancer Res 1984; 44: 5432–8.
Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 1989; 7: 1748–56.
Chatelut E, Canal P, Brunner V, et al. Prediction of carboplatin clearance from standard morphological and biological patient characteristics. J Natl Cancer Inst 1995; 87: 573–80.
Sørensen BT, Strömgren A, Jakobsen P, et al. Alimited sampling method for estimation of the carboplatin area under the curve. Cancer Chemother Pharmacol 1993; 31: 324–7.
Ghazal-Aswad S, Calvert AH, Newell DR. A single-sample assay for the estimation of the area under the free carboplatin plasma concentration versus time curve. Cancer Chemother Pharmacol 1996; 37: 429–34.
Asai G, Ando Y, Saka H, et al. Estimation of the area under the concentration-versus-time curve of carboplatin following irinotecan using a limited sampling model. Eur J Clin Pharmacol 1998; 54: 725–7.
Egorin MJ, Van Echo DA, Olman EA, et al. Prospective validation of a pharmacologically based dosing scheme for the cis-diaminedichloroplatinum (II) analogue diamminecyclobutane-dicarboxylatoplatinum. Cancer Res 1985; 45: 6502–6.
Belani CP, Egorin MJ, Abrams JS, et al. A novel pharmacody-namically based approach to dose optimization of carboplatin when used in combination with etoposide. J Clin Oncol 1989; 7: 1896–902.
Okamoto H, Nagatomo A, Kunitoh H, et al. Prediction of carboplatin clearance calculated by patient characteristics or 24-hour creatinine clearance: a comparison of the performance of three formulae. Cancer Chemother Pharmacol 1998; 42: 307–12.
Newell DR, Siddik ZH, Gumbrell LA, et al. Plasma free platinum pharmacokinetics in patients treated with high dose carboplatin. Eur J Cancer Clin Oncol 1987; 23: 1399–405.
Groen HJM, van der Leest AHD, de Vries EGE, et al. Continuous carboplatin infusion during 6 weeks’ radiotherapy in locally inoperable non-small-cell lung cancer: a phase I and pharmacokinetic study. Br J Cancer 1995; 72: 992–7.
Jodrell DI, Egorin MJ, Canetta RM, et al. Relationships between carboplatin exposure and tumor response and toxicity in patients with ovarian cancer. J Clin Oncol 1992; 10: 520–8.
Lind MJ, Ghazal-Aswad S, Gumbrell L, et al. Phase I study of pharmacologically based dosing of carboplatin with filgrastim support in women with epithelial ovarian cancer. J Clin Oncol 1996; 14: 800–5.
Gore M, Mainwaring P, A’Hern R, et al. Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. J Clin Oncol 1998; 16: 2426–34.
Jakobsen A, Bertelsen K, Andersen JE, et al. Dose-effect study of carboplatin in ovarian cancer: a Danish Ovarian Cancer Group Study. J Clin Oncol 1997; 15: 193–8.
Shea TC, Flaherty M, Elias A, et al. A phase I and pharmaco-kinetic study of carboplatin and autologous bone marrow support. J Clin Oncol 1989; 7: 651–61.
Ghazal-Aswad S, Tilby MJ, Lind M, et al. Pharmacokinetically guided dose escalation of carboplatin in epithelial ovarian cancer: effect on drug-plasma AUC and peripheral blood drug-DNAadduct levels. Ann Oncol 1999; 10: 329–34.
Kinowski J-M, Bressole F, Rodier M, et al. A limited sampling model with bayesian estimation to determine inulin pharmacokinetics using the population data modelling program P-Pharm. Clin Drug Invest 1995; 9: 260–9.
Daugaard G, Rossing N, Rorth M. Effects of cisplatin on different measures of glomerular function in the human kidney with special emphasis on high-dose. Cancer Chemother Pharmacol 1988; 21 (2): 163–7.
Sørensen BT, Strömgren A, Jakobsen P, et al. Is creatinine clear-ance a sufficient measure for GFR in carboplatin dose calculation [abstract]? Eur J Cancer 1993; 29 Suppl. 6: S110.
Calvert AH, Boddy A, Bailey NP, et al. Carboplatin in combination with paclitaxel in advanced ovarian cancer: dose determination and pharmacokinetic and pharmacodynamic interactions. Semin Oncol 1995; 22 Suppl. 12: 91–100.
van Warmerdam LJC, Rodenhuis S, ten Bokkel Huinink WW, et al. The use of the Calvert formula to determine the optimal carboplatin dosage. J Cancer Res Clin Oncol 1995; 121: 478–86.
Shea T, Graham M, Bernard S, et al. A clinical and pharmacokinetic study of high-dose carboplatin, paclitaxel, granulo-cyte colony-stimulating factor, and peripheral blood stem cells in patients with unresectable or metastatic cancer. Semin Oncol 1995; 22 Suppl. 12: 80–5.
Kearns CM, Belani CP, Erkmen K, et al. Pharmacokinetics of paclitaxel and carboplatin in combination. Semin Oncol 1995; 22 Suppl. 12: 1–7.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41.
Jelliffe RW. Creatinine clearance: bedside estimation. Ann Intern Med 1973; 79: 604–5.
van Warmerdam LJC, Rodenhuis S, ten Bokkel Huinink WW, et al. Evaluation of formulas using the serum creatinine level to calculate the optimal dosage of carboplatin. Cancer Chemother Pharmacol 1996; 37: 266–70.
Fujiwara Y, Takahashi T, Yamakido M, et al. Prediction of carboplatin clearance from standard morphological and biological patient characteristics [letter]. J Natl Cancer Inst 1997; 89: 260–1.
Perrone RD, Madias NE, Levey AS. Serum creatinine as an index of renal function: new insights into old concepts. Clin Chem 1992; 38: 1933–53.
Calvert AH. A review of the pharmacokinetics and pharmaco-dynamics of combination carboplatin/paclitaxel. Semin Oncol 1997; 24 Suppl. 2: 85–90.
Ando Y, Minami H, Saka H, et al. Adjustment of creatinine clearance improves accuracy of Calvert’s formula for carboplatin dosing. Br J Cancer 1997; 76: 1067–71.
Martin L, Chatelut E, Boneu A, et al. Improvement of the Cockcroft-Gault equation for predicting glomerular filtration in cancer patients. Bull Cancer 1998; 85: 631–6.
Wright JG, Calvert AH, Highley MS, et al. Accurate prediction of renal function for carboplatin dosing [abstract]. Proc Am Assoc Cancer Res 1999; 40: 384.
Langer CJ, Leighton JC, Comis RL, et al. Paclitaxel and carboplatin in combination in the treatment of advanced non-small cell lung cancer: a phase II toxicity, response, and survival analysis. J Clin Oncol 1995; 13: 1860–70.
Reyno LM, Egorin MJ, Canetta RM, et al. Impact of cyclophos-phamide on relationships between carboplatin exposure and response or toxicity when used in the treatment of advanced ovarian cancer. J Clin Oncol 1993; 11: 1156–64.
Harland SJ, Gumbrell LA, Horwich A. Carboplatin dose in combination chemotherapy for testicular cancer. Eur J Cancer 1991; 27: 691–5.
Horwich A, Dearnaley DP, Nicholls J, et al. Effectiveness of carboplatin, etoposide, and bleomycin combination chemotherapy in good-prognosis metastatic testicular nonseminomatous germ cell tumors. J Clin Oncol 1991; 9: 62–9.
Krigel RL, Palackdharry CS, Padavic K, et al. Ifosfamide, carboplatin, and etoposide plus granulocyte-macrophage colony-stimulating factor: a phase I study with apparent activity in non-small-cell lung cancer. J Clin Oncol 1994; 12: 1251–8.
Green JA, Smith K. Dose intensity of carboplatin in combination with cyclophosphamide or ifosfamide. Cancer Chemother Pharmacol 1990; 26 Suppl.: 22–5.
Obasaju CK, Johnson SW, Rogatko A. Evaluation of carboplatin pharmacokinetics in the absence and presence of paclitaxel. Clin Cancer Res 1996; 2: 549–52.
Belani CP, Kearns CM, Zuhowski EG, et al. Phase I trial, including pharmacokinetic and pharmacodynamic correlations, of combination paclitaxel and carboplatin in patients with metastatic non-small-cell lung cancer. J Clin Oncol 1999; 17: 676–84.
Childs WJ, Nicholls EJ, Horwich A. The optimisation of carboplatin dose in carboplatin, etoposide and bleomycin combination chemotherapy for good prognosis metastatic non-seminomatous germ cell tumours of the testis. Ann Oncol 1992; 3: 291–6.
Siddiqui N, Boddy AV, Thomas HD, et al. A clinical and pharmacokinetic study of the combination of carboplatin and paclitaxel for epithelial ovarian cancer. Br J Cancer 1997; 75: 287–94.
Okamoto H, Nagatomo A, Kunitoh H, et al. A phase I clinical and pharmacologie study of a carboplatin and irinotecan regimen combined with recombinant human granulocyte-colony stimulating factor in the treatment of patients with advanced nonsmall cell lung cancer. Cancer 1998; 82: 2166–72.
Kattan J, Mahjoubi M, Droz JP, et al. High failure rate of carboplatin-etoposide combination in good risknon-seminomatous germ cell tumours. Eur J Cancer 1993; 29A: 1504–9.
Meerpohl HG, du Bois A, Luck HJ, et al. Paclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer: a phase I trial. Semin Oncol 1997; 24 Suppl. 2: 17–22.
Rowinsky EK, Flood WA, Sartorius SE, et al. Phase I study of paclitaxel as a 3-hour infusion followed by carboplatin in untreated patients with stage IV non-small cell lung cancer. Semin Oncol 1995; 22 Suppl. 9: 48–54.
Huizing MT, Giaccone G, Van Warmerdam LJC, et al. Pharma-cokinetics of paclitaxel and carboplatin in a dose-escalating and sequencing study in patients with non-small-cell lung cancer. J Clin Oncol 1997; 15: 317–29.
Sadan S, Barjorin DF, Mazumdar M, et al. Correlation of carboplatin (CBDCA) area under the curve (AUC) with myelo-suppression and infection in germ cell tumor (GCT) Patients (PTS) [abstract]. Proc Am Soc Clin Oncol 1993; 12: 159.
Chatelut E, Chevreau C, Brunner V, et al. A pharmacologically guided phase I study of carboplatin in combination with methotrexate and vinblastine in advanced urothelial cancer. Cancer Chemother Pharmacol 1995; 35: 391–6.
Sculier JP, Paesmans M, Thiriaux J, et al. Acomparison of methods of calculation for estimating carboplatin AUC with a retrospective pharmacokinetic-pharmacodynamic analysis in patients with advanced non-small cell lung cancer. Eur J Cancer 1999; 35: 1314–9.
Huizing MT, Keung ACF, Rosing H, et al. Pharmacokinetics of paclitaxel and metabolites in a randomized comparative study in platinum-pretreated ovarian cancer patients. J Clin Oncol 1993; 11: 2127–35.
Calvert AH. Dose optimisation of carboplatin in adults. Anti-cancer Res 1994; 14: 2273–8.
D’Argenio DZ. Optimal sampling times for pharmacokinetic experiments. J Pharmacokinet Biopharm 1981; 9: 739–56.
van Warmerdam LJC, Rodenhuis S, van Tellingen O, et al. Validation of a limited sampling model for carboplatin in a high dose chemotherapy combination. Cancer Chemother Pharmacol 1994; 35: 179–81.
van Warmerdam LJC, Ten Bokkel Huinink WW, Maes RAA, et al. Limited sampling models for anticancer agents. J Cancer Res Clin Oncol 1994; 120: 427–33.
Nannan Panday VR, van Warmerdam LJC, Huizing MT, et al. A limited sampling model for the pharmacokinetics of carboplatin administered in combination with paclitaxel. J Cancer Res Clin Oncol 1999; 125: 615–20.
Nannan Panday VR, van Warmerdam LJC, Huizing MT, et al. A single 24-hour plasma sample does not predict the carboplatin AUC from carboplatin-paclitaxel combinations or from a high-dose carboplatin-thiotepa-cyclophosphamide regimen. Cancer Chemother Pharmacol 1999; 43: 435–8.
Guillet P, Monjanel S, Nicoara A, et al. A bayesian dosing method for carboplatin given by continuous infusion for 120h. Cancer Chemother Pharmacol 1997; 40: 143–9.
Duffull SB, Begg EJ, Robinson BA, et al. Asequential Bayesian algorithm for dose individualisation of carboplatin. Cancer Chemother Pharmacol 1997; 39: 317–26.
Huitema ADR, Mathôt RAA, Tibben MM, et al. Validation of techniques for the prediction of carboplatin exposure: application of Bayesian methods. Clin Pharmacol Ther 2000; 67: 621–30.
Jodrell DI, Murray LS, Hawtof J, et al. Acomparison of methods for limited-sampling strategy design using data from a phase I trial of the anthrapyrazole DuP-941. Cancer Chemother Pharmacol 1996; 37: 356–62.
van Warmerdam LJC, van den Bemt BJF, Ten Bokkel Huinink WW, et al. Dose individualisation in cancer chemotherapy: pharmacokinetic and pharmacodynamic relationships. Cancer Res Ther Control 1995; 4: 277–91.
Grochow LB, Jones RJ, Brundrett RB, et al. Pharmacokinetics of busulfan: correlation with veno-occlusive disease in patients undergoing bone marrow transplantation. Cancer Chemother Pharmacol 1989; 25: 55–61.
Dix SP, Wingard JR, Mullins RE, et al. Association of busulfan area under the curve with veno-occlusive disease following BMT. Bone Marrow Transplant 1996; 17: 225–30.
Vassal G, Koscielny S, Challine D, et al. Busulfan disposition and hepatic veno-occlusive disease in children undergoing bone marrow transplantation. Cancer Chemother Pharmacol 1996; 37: 247–53.
Sonnichsen D, Ribeiro R, Luo X, et al. Pharmacokinetics and pharmacodynamics of 21 day continuous oral etoposide in pédiatrie patients with solid tumors. Clin Pharmacol Ther 1995; 58: 99–107.
Elbaek K, Ebbehoj E, Jakobsen A, et al. Pharmacokinetics of oral idarubicin in breast cancer patients with reference to antitumor activity and side effects. Clin Pharmacol Ther 1989; 45 (6): 627–34.
Dodion P, De Valeriola D, Crespeigne N, et al. Phase I clinical and pharmacokinetic trial of oral menogaril administered on three consecutive days. Eur J Cancer Clin Oncol 1988; 24: 1019–26.
Schellens JHM, Eckardt JR, Creemers GJ, et al. Pharmacokinetics (PK), clinical pharmacodynamics (PD) and safety of chronic oral topotecan (T) in a phase I study [abstract]. Proc Am Soc Clin Oncol 1995; 14: 457.
Creemers GF, Gerrits CJH, Eckardt JR, et al. Phase I and pharmacologie study of oral topotecan administered twice daily for 21 days to adult patients with solid tumors. J Clin Oncol 1997; 15: 1087–93.
Reece PA, Stafford I, Russell J, et al. Creatinine clearance as a predictor of ultrafilterable platinum disposition in cancer patients treated with cisplatin: relationship between peak ultrafilterable platinum plasma levels and nephrotoxicity. J Clin Oncol 1987; 5: 304–9.
Schellens JHM, Ma J, Planting ASTh, et al. Relationship between the exposure to cisplatin, DNA-adduct formation in leucocytes and tumour response in patients with solid tumours. Br J Cancer 1996; 73: 1569–75.
Ayash LJ, Wright JE, Tretyakov O, et al. Cyclophosphamide pharmacokinetics: correlation with cardiac toxicity and tumor response. J Clin Oncol 1992; 10: 995–1000.
Bruno R, Hille D, Riva A, et al. Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer. J Clin Oncol 1998; 1: 187–196.
Jakobsen P, Bastholt L, Dalmark M, et al. A randomized study of epirubicin at four different dose levels in advanced breast cancer: feasibility of my elo toxicity prediction through single blood-sample measurement. Cancer Chemother Pharmacol 1991; 28: 465–9.
Miller AA, Stewart CF, Tolley EA. Clinical pharmacodynamics of continuous-infusion etoposide. Cancer Chemother Pharmacol 1990; 25: 361–6.
Desoize B, Maréchal F, Cattan A. Clinical pharmacokinetics of etoposide during 120 hours continuous infusions in solid tumours. Br J Cancer 1990; 62: 840–1.
Miller AA, Tolley EA, Niell HB, et al. Pharmacodynamics of three daily infusions of etoposide in patients with extensive-stage small-cell lung cancer. Cancer Chemother Pharmacol 1992; 31: 161–6.
Budman DR, Igwemezie L, Kaul S, et al. Pharmacodynamic findings with etoposide phosphate (BMY 4081), a water soluble prodrug [abstract]. Proc Am Soc Clin Oncol 1994; 13: 146.
Goldberg JA, Kerr DJ, Willmott N, et al. Pharmaokinetics and pharmacodynamics of locoregional 5-fluorouracil (5FU) in advanced colorectal liver métastases. Br J Cancer 1988; 57: 186–9.
van Groeningen CJ, Pinedo HM, Heddes J, et al. Pharmaco-kinetics of 5-fluorouracil assessed with a sensitive mass spectrometric method in patients on a dose escalation schedule. Cancer Res 1988; 48: 6956–61.
Thyss A, Milano G, Renée N, et al. Clinical pharmacokinetic study of 5-FU in continuous 5-day infusions for head and neck cancer. Cancer Chemother Pharmacol 1986; 16: 64–6.
Santini J, Milano G, Thyss A, et al. 5-FU therapeutic monitoring with dose adjustment leads to an improved therapeutic index in head and neck cancer. Br J Cancer 1989; 59: 287–90.
Milano G, Etienne MC, Renée N, et al. Relationship between fluorouracil systemic exposure and tumor response and patient survival. J Clin Oncol 1994; 12: 1291–5.
Vokes EE, Mick R, Kies MS, et al. Pharmacodynamics of fluorouracil-based induction chemotherapy in advanced head and neck cancer. J Clin Oncol 1996; 14: 1664–71.
Gamelin EC, Danquechin-Dorval EM, Dumesnil YF, et al. Relationship between 5-fluorouracil (5-FU) dose intensity and therapeutic response in patients with advanced colorectal cancer receiving infusional therapy containing 5-FU. Cancer 1996; 77: 441–51.
Gamelin E, Boisdron-Celle M, Delva R, et al. Long-term weekly treatment of colorectal metastatic cancer with fluorouracil and leucovorin: results of a multicentric prospective trial of fluorouracil dosage optimization by pharmacokinetic monitoring in 152 patients. J Clin Oncol 1998; 16: 1470–8.
Rowinsky EK, Ettinger DS, McGuire WP, et al. Prolonged infusion of hexamethylene bisacetamide: a phase I and pharmacological study. Cancer Res 1987; 47: 5788–95.
Egorin MJ, Sigman LM, Van Echo DA, et al. Phase I clinical and pharmacokinetic study of hexamethylene bisacetamide (NSC 95580) administered as a five-day continuous infusion. Cancer Res 1987; 47: 617–23.
Conley BA, Forrest A, Egorin MJ, et al. Phase I trial using adaptive control dosing of hexamethylene bisacetamide (NSC 95580). Cancer Res 1989; 49: 3436–40.
Gianni L, Vigano L, Surbone A, et al. Pharmacology and clinical toxicity of 4′-iodo-4′-deoxydoxorubicin: an example of successful application of pharmacokinetics to dose escalation in phase I trials. J Natl Cancer Inst 1990; 82: 469–77.
Robert J, Armand JP, Huet S, et al. Pharmacokinetics and metabolism of 4′-iodo-4′-deoxy-doxorubicin in humans. J Clin Oncol 1992; 10: 1183–90.
Egorin MJ, Van Echo DA, Whitacre MY, et al. Human pharmacokinetics, excretion, and metabolism of the anthracycline antibiotic menogaril (7-OMEN, NSC 269148) and their correlation with clinical toxicities. Cancer Res 1986; 46: 1513–20.
Egorin MJ, Conley BA, Forrest A, et al. Phase I study and pharmacokinetics of menogaril (NSC 269148) in patients with hepatic dysfunction. Cancer Res 1987; 47: 6104–10.
Longnecker SM, Donehower RC, Cates AE, et al. High-performance liquid Chromatographic assay for taxol in human plasma and urine and pharmacokinetics in a phase I trial. Cancer Treat Rep 1987; 71: 53–9.
Sonnichsen DS, Hurwitz CA, Pratt CB, et al. Saturable pharmacokinetics and paclitaxel pharmacodynamics in children with solid tumors. J Clin Oncol 1994; 12: 532–8.
Evans WE, Rodman JH, Relling MV, et al. Differences in teniposide disposition and pharmacodynamics in patients with newly diagnosed and relapsed acute lymphocytic leukemia. J Pharmacol Exp Ther 1992; 260: 71–7.
Rodman JH, Furman WL, Sunderland M, et al. Escalating teniposide systemic exposure to increase dose intensity for pediatric cancer patients. J Clin Oncol 1993; 11: 287–93.
Stewart CF, Baker SD, Heideman RL, et al. Clinical pharmacodynamics of continuous infusion topotecan in children: systemic exposure predicts hématologic toxicity. J Clin Oncol 1994; 12: 1946–54.
Haas NB, LaCreta FP, Walczak J, et al. Phase I/pharmacokinetic study of topotecan by 24-hour continuous infusion weekly. Cancer Res 1994; 54: 1220–6.
van Warmerdam LJC, Verweij J, Schellens JHM, et al. Pharmacokinetics and pharmacodynamics of topotecan administered daily for 5 days every 3 weeks. Cancer Chemother Pharmacol 1995; 35: 237–45.
Schiller JH, Kim K, Hutson P, et al. Phase II study of topotecan in patients with extensive-stage small-cell carcinoma of the lung: an Eastern Cooperative Oncology Group trial. J Clin Oncol 1996; 14: 2345–52.
van Warmerdam LJC, Creemers GJ, Rodenhuis S, et al. Pharmacokinetics and pharmacodynamics of topotecan given on a daily-times-five schedule in phase II clinical trials using a limited-sampling procedure. Cancer Chemother Pharmacol 1996; 38: 254–60.
Herben VMM, ten Bokkel Huinink WW, Dubbelman AC, et al. Phase I and pharmacological study of sequential intravenous topotecan and oral etoposide. Br J Cancer 1997; 76: 1500–8.
Milano G, Roman P, Khater R, et al. Dose versus pharmacokinetics for predicting tolerance to 5-day continuous infusion of 5-FU. Int J Cancer 1988; 41: 537–41.
Grochow LB. Busulfan disposition: the role of therapeutic monitoring in bone marrow transplantation induction regimens. Semin Oncol 1993; 4: 18–25.
Decker J, Lindley C, McCune J, et al. Busulfan test dose area under the curve (AUC) predicts dose required to achieve targeted therapeutic concentration in bone marrow transplant (BMT) patients [abstract]. Proc Am Soc Clin Oncol 1998; 17: 189.
Yeager AM, Wagner JE, Graham ML, et al. Optimization of busulfan dosage in children undergoing bone marrow transplantation: a pharmacokinetic study of dose escalation. Blood 1992; 80: 2425–8.
Nagai N, Kinoshita M, Ogata H, et al. Relationship between pharmacokinetics of unchanged cisplatin and nephrotoxicity after intravenous infusions of cisplatin to cancer patients. Cancer Chemother Pharmacol 1996; 39: 131–7.
Campbell AB, Kaiman SM, Jacobs C. Plasma platinum levels: relationship to cisplatin dose and nephrotoxicity. Cancer Treat Rep 1983; 67: 169–72.
Reed E, Ozols RF, Tarone R, et al. Platinum-DNA adducts in leukocyte DNA correlate with disease response in ovarian cancer patients receiving platinum-based chemotherapy. Proc Natl Acad Sci USA 1987; 84: 5024–8.
Reed E, Ostchega Y, Steinberg SM, et al. Evaluation of platinum-DNA adduct levels relative to known prognostic variables in a cohort of ovarian cancer patients. Cancer Res 1990; 50: 2256–60.
Reed E, Ozols RF, Tarone R, et al. The measurement of cisplatin-DNA adduct levels in testicular cancer patients. Carcinogenesis 1988; 9: 1909–11.
Fichtinger-Schepman AMJ, van der Velde SD, van Dijk-Knijnenburg HCM, et al. Kinetics of the formation and removal of cisplatin-DNA adducts in blood cells and tumor tissue of cancer patients receiving chemotherapy: comparison with in vitro adduct formation. Cancer Res 1990; 50: 7887–94.
Parker RJ, Gill I, Tarone R, et al. Platinum-DNA damage in leukocyte DNA of patients receiving carboplatin and cisplatin chemotherapy, measured by atomic absorption spectrometry. Carcinogenesis 1991; 12: 1253–8.
Egorin MJ, Forrest A, Belani CP, et al. Alimited sampling strategy for cyclophosphamide pharmacokinetics. Cancer Res 1989; 49: 3129–33.
Lichtman SM, Ratain MJ, Van Echo DA, et al. Phase I trial of granulocyte-macrophage colony-stimulating factor plus high-dose cyclophosphamide given every 2 weeks: a cancer and leukemia group B study. J Natl Cancer Inst 1993; 85: 1319–26.
van Hoesel QGCM, Verweij J, Catimel G, et al. Phase II study with docetaxel (Taxotere®) in advanced soft tissue sarcomas of the adult. Ann Oncol 1994; 5: 539–42.
ten Bokkel Huinink WW, Prove AM, Piccart M, et al. Aphase II trial with docetaxel (Taxotere®) in second line treatment with chemotherapy for advanced breast cancer. Ann Oncol 1994; 5: 527–32.
Catimel G, Verweij J, Matthijssen V, et al. Docetaxel (Taxotere®): an active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. Ann Oncol 1994; 5: 533–7.
Hudis CA, Seidman AD, Crown JPA, et al. Phase II and pharmacologic study of docetaxel as initial chemotherapy for metastatic breast cancer. J Clin Oncol 1996; 14: 58–65.
Lowis SP, Pearson ADJ, Newell DR, et al. Etoposide pharmacokinetics in children: the development and prospective validation of a dosing equation. Cancer Res 1993; 53: 4881–9.
Lowis SP, Price L, Pearson ADJ, et al. A study of the feasibility and accuracy of pharmacokinetically guided etoposide dosing in children. Br J Cancer 1998; 77: 2318–23.
Joel SP, Ellis P, O’Byrne K, et al. Therapeutic monitoring of continuous infusion etoposide in small-cell lung cancer. J Clin Oncol 1996; 14: 1903–12.
Trump DL, Egorin MJ, Forrest A, et al. Pharmacokinetic and pharmacodynamic analysis of fluorouracil during 72-hour continuous infusion with and without dipyridamole. J Clin Oncol 1991; 9: 2027–35.
Ychou M, Duffour J, Pinguet F, et al. Individual 5FU-dose adaptation schedule using bimonthly pharmacokinetically modulated LV5FU2 regimen: a feasibility study in patients with advanced colorectal cancer. Anticancer Res 1999; 19: 2229–36.
Bressole F, Joulia JM, Pinguet F, et al. Circadian rhythm of 5-fluorouracil population pharmacokinetics in patients with metastatic colorectal cancer. Cancer Chemother Pharmacol 1999; 44: 295–302.
Conley BA, Egorin MJ, Sinibaldi V, et al. Approaches to optimal dosing of hexamethylene bisacetamide. Cancer Chemother Pharmacol 1992; 31: 37–45.
Smith DB, Margison JM, Lucas SB, et al. Clinical pharmacology of oral and intravenous 4-demethoxydaunorubicin. Cancer Chemother Pharmacol 1987; 19: 138–42.
Schleyer E, Kuhn S, Ruhrs H, et al. Oral idarubicin pharmacokinetics: correlation of trough level with idarubicin area under curve. Leukemia 1996; 10: 707–12.
Sessa C, Calabresi F, Cavalli F, et al. Phase II studies of 4′-iodo-4′-deoxydoxorubicin in advanced non-small cell lung, colon and breast cancers. Ann Oncol 1991; 2: 727–31.
Sörensen JB, Stenbygaard L, Drivsholm L, et al. Phase II study of 4′-iodo-4′-deoxydoxorubicin in non-resectable non-small-cell lung cancer. Cancer Chemother Pharmacol 1993; 32: 399–402.
Gianni L, Kearns CM, Gianni A, et al. Nonlinear pharmacokinetics and metabolism of paclitaxel and its pharmacokinetic/pharmacodynamic relationships in humans. J Clin Oncol 1995; 13: 180–90.
Petros WP, Rodman JH, Mirro J, et al. Pharmacokinetics of continuous-infusion amsacrine and teniposide for the treatment of relapsed childhood acute nonlymphocytic leukemia. Cancer Chemother Pharmacol 1991; 27: 397–400.
Rodman JH, Abromowitch M, Sinkule JA, et al. Clinical pharmacodynamics of continuous infusion teniposide: systemic exposure as a determinant of response in a phase I trial. J Clin Oncol 1987; 5: 1007–14.
van Warmerdam LJC, Verweij J, Rosing H, et al. Limited sampling models for topotecan pharmacokinetics. Ann Oncol 1994; 5: 259–64.
Stoller RG, Hände KR, Jacobs SA, et al. Use of plasma phar-macokinetics to predict and prevent methotrexate toxicity. N Engl J Med 1977; 297: 630–4.
Favre R, Monjanel S, Alfonsi M, et al. High-dose methotrexate: a clinical and pharmacokinetic evaluation. Cancer Chemother Pharmacol 1982; 9: 156–60.
Widemann BC, Balis FM, Murphy RF, et al. CarboxypeptidaseG2, thymidine, and leucovorin rescue in cancer patients with methotrexate-induced renal dysfunction. J Clin Oncol 1997; 15: 2125–34.
Relling MV, Fairclough D, Ayers D, et al. Patient characteristics associated with high-risk methotrexate concentrations and toxicity. J Clin Oncol 1994; 12: 1667–72.
Monjanel S, Rigault JP, Cano JP, et al. High-dose methotrexate: preliminary evaluation of a pharmacokinetic approach. Cancer Chemother Pharmacol 1979; 3: 189–96.
Crom W, Mauer E, Greene W, et al. Relation between cisplatin ototoxicity and platinum accumulation in plasma [abstract]. Proc Am Assoc Cancer Res 1984; 3: 28.
Schilsky RL, O’Laughlin K, Ratain MJ. Phase I clinical and pharmacology study of thymidine (NSC 21548) and cisdiamminedichloroplatinum(II) in patients with advanced cancer. Cancer Res 1986; 46: 4184–8.
Bennett CL, Sinkule JA, Schilsky RL, et al. Phase I clinical and pharmacological study of 72-hour continuous infusion of etoposide in patients with advanced cancer. Cancer Res 1987; 47: 1952–6.
Au JS, Rustum YM, Ledesma EJ, et al. Clinical pharmacological studies of concurrent infusion of 5-fluorouracil and thymidine in the treatment of colorectal carcinomas. Cancer Res 1982; 42: 2930–7.
Ackland SP, Ratain MJ, Vogelzang NJ, et al. Pharmacokinetics and pharmacodynamics of long-term continuous-infusion doxorubicin. Clin Pharmacol Ther 1989; 45: 340–7.
Wiernik PH, Schwartz EL, Strauman JJ, et al. Phase I clinical and pharmacokinetic study of taxol. Cancer Res 1987; 47: 2486–93.
Ratain MJ, Vogelzang NJ. Phase I and pharmacologic study of vinblastine by prolonged continuous infusion. Cancer Res 1986; 44: 4827–30.
Mick R, Ratain MJ. Modeling interpatient pharmacodynamic variability of etoposide. J Natl Cancer Inst 1991; 83: 1560–4.
Rowinsky EK, Ettinger DS, Grochow LB, et al. Phase I and pharmacologic study of hexamethylene bisacetamide in patients with advanced cancer. J Clin Oncol 1986; 4: 1835–44.
Vozeh S, Steimer JL, Rowland M, et al. The use of population pharmacokinetics in drug development. Clin Pharmacokinet 1996; 30 (2): 81–93.
Duffull SB, Robinson BA. Clinical pharmacokinetics and dose optimisation of carboplatin. Clin Pharmacokinet 1997; 33: 161–83.
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van den Bongard, H.J.G.D., Mathôt, R.A.A., Beijnen, J.H. et al. Pharmacokinetically Guided Administration of Chemotherapeutic Agents. Clin Pharmacokinet 39, 345–367 (2000). https://doi.org/10.2165/00003088-200039050-00004
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DOI: https://doi.org/10.2165/00003088-200039050-00004