Abstract
Thrombocytopenia induced by carboplatin combined with etoposide for elderly lung cancer patients was analyzed in relation to the predicted thrombocytopenia by the equations advocated by Egorin et al. and Taguchi et al. The thrombocytopenia actually observed was strongly correlated with and significantly more severe than that predicted if carboplatin had been administered as a single agent. The AUC (area under the curve) of carboplatin predicted by Calvert's equation significantly affected the degree of thrombocytopenia. These data suggested that dosing of carboplatin should be determined individually on the basis of renal function, as recommended earlier. The reason for the enhancement of thrombocytopenia is yet to be determined in future trials.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- SCLC :
-
small-cell lung cancer
- NSCLC :
-
non-small-cell lung cancer
- AUC :
-
area under the curve (dose/clearance)
- GFR :
-
glomerular filtration rate
- LD :
-
limited disease
- ED :
-
extensive disease
References
Avenarius HJ, Freund M, Deinhardt J, Poliwoda H (1992) Effect of recombinant human granulocyte colony-stimulating factor (rhGCSF) on circulating platelets. Ann Hematol 65:6–9
Balducci L, Parker M, Sexton W, Tantranond P (1989) Pharmacology of antineoplastic agents in elderly patients. Semin Oncol 16:76–84
Begg CB, Carbone PP (1986) Clinical trials and drug toxicity in the elderly. Cancer 52:1986–1992
Belani CP, Egorin MJ, Abrams JS, Hiponia D, Eisenberger M, Aisner J, Echo DA van (1989) A novel pharmacodynamically based approach to dose optimization of carboplatin when used in combination with etoposide. J Clin Oncol 7:1896–1902
Bishop JF, Raghavan D, Stuart-Harris R, Morstyn G, Aroney R, Kefford R, Yuen K, Lee J, Gianoutsos P, Olver IN, Zalcberg J, Ball D, Bull C, Fox R (1987) Carboplatin (CBDCA, JM-8) and VP-16-213 in previously untreated patients with small-cell lung cancer. J Clin Oncol 5:1574–1578
Bonomi PD, Finkelstein DM, Ruchdeschel JC, Blum RH, Green MD, Mason B, Hahn R, Tormey DC, Harris J, Comis R, Glick J (1989) Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small cell lung cancer: a study of the Eastern Cooperative Oncology Group. J Clin Oncol 7:1602–1613
Calvert AH, Newell DR, Gumbrell LA, O'Reilly S, Burnell M, Boxall FE, Siddik ZH, Judson IR, Gore ME, Wiltshaw E (1989) Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 17:1748–1756
Egorin MJ, Echo DA van, Tipping SJ, Olman EA, Whitacre MY, Thompson BW, Aisner J (1984) Pharmocokinetics and dosage reduction ofcis-diammine(1,1-cyclobutanedicarboxylato)platinum in patients with impaired real function. Cancer Res 44: 5432–5438
Egorin MJ, Echo DA van, Olman EA, Whitacre MY, Forrest A, Aisner J (1985) Prospective validation of a pharmacologically based dosing scheme for thecis-diamminedichloroplatinum(II) analogue diamminecyclobutanedicarboxylatoplatinum. Cancer Res 45:6502–6506
Gatzemeier U, Heckmayr M, Hossfeld DK, Zschaber R, Achterrath W (1990a) Phase II study of carboplatin in untreated, inoperable non-small-cell lung cancer. Cancer Chemother Pharmacol 26: 369–372
Gatzemeier U, Heckmayr M, Neuhauss R, Hossfeld D, Achterrath W, Lenaz L (1990b) Phase II studies with carboplatin in non-small cell lung cancer. Semin Oncol 17:25–31
Gatzemeier U, Hossfeld DK, Neuhauss R, Reck M, Achterrath W, Lenaz L (1992) Combination chemotherapy with carboplatin, etoposide, and vincristine as first-line treatment in small-cell lung cancer. J Clin Oncol 10:818–823
Hande KR (1993) Pharmacologic-based dosing of carboplatin: a better method. J Clin Oncol 11:2295–2296
Issell BF, Crooke ST (1979) Etoposide (VP-16-213). Cancer Treat Rev 6:107–124
Kennedy BJ (1991) Needed: clinical trials for older patients. J Clin Oncol 9:718–720
Klastersky J, Sculier JP, Lacroix H, Dabouis G, Bureau G, Libert P, Richez M, Ravez P, Vandermoten G, Thiriaux J, Cordier R, Finet C, Berchier MC, Sergysels R, Mommen P, Paesmans M (1990) A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861. J Clin Oncol 8:1556–1562
Lindermann A, Herrmann F, Oster W, Haffner G, Meyenburg W, Souza LM, Mertelsmann R (1989) Hematologic effects of recombinant human granulocyte colony-stimulating factor in patients with malignancy. Blood 74:2644–51
Mizushima Y, Morikage T, Kuwahara T, Yano S (1990) Effect of granulocyte colony-stimulating factor on hematopoietic injury induced by anticancer drugs in mice. J Biol Response Mod 9: 576–583
Newell DR, Pearson ADJ, Balmanno K, Price L, Wyllie RA, Keir M, Calvert AH, Lewis IJ, Pinkerton CR, Stevens CG (1993) Carboplatin pharmacokinetics in children: the development of a padiatric dosing formula. J Clin Oncol 11:2314–2323
Pflüger KH, Hahn M, Holz JB, Schmidt L, Köhl P, Fritsch HW, Jungclas H, Havemann K (1993) Pharmacokinetics of etoposide: correlation of pharmacokinetic parameters with clinical conditions. Cancer Chemother Pharmacol 31:350–356
Poplin E, Thompson B, Whitacre M, Aisner J (1987) Small cell carcinoma of the lung: influence of age on treatment outcome. Cancer Treat Rep 71:291–296
Reyno LM, Egorin MJ, Canetto RM, Jodrell DI, Swenerton KD, Pater JL, Burrows JN, Novak MJ, Sridhara R (1993) Impact of cyclophosphamide on relationship between carboplatin exposure and response or toxicity when used in the treatment of advanced ovarian cancer. J Clin Oncol 11:1156–1164
Shimoda K, Okamura S, Harada N, Kondo S, Okamura T, Niho Y (1993) Identification of a functional receptor for granulocyte colony-stimulating factor on platelets. J Clin Invest 91: 1310–1313
Smith IE, Evans BD, Gore ME, Vincent MD, Repetto L, Yarnold JR, Ford HT (1987) Carboplatin (Paraplatin; JM8) and etoposide (VP-16) as first-line combination therapy for small-cell lung cancer. J Clin Oncol 5:185–189
Taguchi J, Saijo N, Miura K, Shinkai T, Eguchi K, Sasaki Y, Tamura T, Sakurai M, Minato K, Fujiwara Y, Nakano H, Nakagawa K, Hong W (1987) Prediction of hematologic toxicity of carboplatin by creatinine clearance rate. Jpn J Cancer Res 78:977–982
Thatcher N, Lind M (1990) Carboplatin in small cell lung cancer. Semin Oncol 17:40–48
Vijgh WJF van der (1991) Clinical pharmacokinetics of carboplatin. Clin Pharmacokinet 21:242–261
Author information
Authors and Affiliations
Additional information
This work was in part supported by a grant from Bristol-Myers Squibb Japan, Tokyo
Rights and permissions
About this article
Cite this article
Shibata, K., Nakatsumi, Y., Kasahara, K. et al. Analysis of thrombocytopenia due to carboplatin combined with etoposide in elderly patients with lung cancer. J Cancer Res Clin Oncol 122, 437–442 (1996). https://doi.org/10.1007/BF01212885
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01212885