Skip to main content

Advertisement

SpringerLink
Log in

Phase I combination trial of gemcitabine, paclitaxel, and carboplatin in patients with advanced malignancy

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

We performed a phase I trial of carboplatin and paclitaxel in combination with gemcitabine in order to determine the tolerability of this triplet.

Methods

Enrolled in the study were 26 patients with advanced cancer, most with non-small cell lung cancer. The patients received escalating doses of carboplatin and paclitaxel on day 1 and gemcitabine (30-min infusion) on days 1, 8, and 15 of a 28-day treatment cycle. The doses of each drug ranged from an area under the concentration-time curve (AUC) of 5 to 6 for carboplatin, 135 to 175 mg/m2 for paclitaxel, and 300 to 1000 mg/m2 for gemcitabine.

Results

Hematologic toxicity was the most commonly observed toxicity and was dose-limiting. During the first cycle at the recommended phase II dose, there were two instances of grade 4 neutropenia and one instance of grade 4 thrombocytopenia among six patients, none of which was dose-limiting. Cumulative hematologic toxicity emerged in subsequent cycles. Non-hematologic toxicities were mild. Five patients, all with previously untreated non-small-cell lung cancer (NSCLC), had a partial response. Nine patients with NSCLC or upper gastrointestinal malignancies experienced stable disease.

Conclusions

Based on significant neutropenia and thrombocytopenia, the regimen recommended for further study consists of carboplatin AUC 5, paclitaxel 175 mg/m2, and gemcitabine 1000 mg/m2 on a 28-day cycle. The antitumor activity noted suggests that further investigation of this well-tolerated combination in specific tumor types, especially NSCLC, is warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Vermorken JB (2001) The integration of paclitaxel and new platinum compounds in the treatment of advanced ovarian cancer. Int J Gynecol Cancer 11 [Suppl 1]:21–30

    Google Scholar 

  2. Sandler A (2000) Chemotherapy in metastatic non-small-cell lung cancer. Oncology (Huntingt) 14 [7 Suppl 5]:15–27

  3. Waxman J, Wasan H (1994) Platinum-based chemotherapy for bladder cancer. Semin Oncol 21 [5 Suppl 12]:54–60

    Google Scholar 

  4. Forastiere AA (1994) Overview of platinum chemotherapy in head and neck cancer. Semin Oncol 21 [5 Suppl 12]:20–27

    Google Scholar 

  5. Kelly K, Crowley J, Bunn PA Jr, Presant CA, Grevstad PK, Moinpour CM, Ramsey SD, Wozniak AJ, Weiss GR, Moore DF, Israel VK, Livingston RB, Gandara DR (2001) Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol 19:3210–3218

    CAS  PubMed  Google Scholar 

  6. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; The Eastern Cooperative Oncology Group (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92–98

    Google Scholar 

  7. Souglakos J, Mavroudis D, Kakolyris S, Kourousis Ch, Vardakis N, Androulakis N, Agelaki S, Kalbakis K, Tsetis D, Athanasiadis N, Samonis G, Georgoulias V (2002) Triplet combination with irinotecan plus oxaliplatin plus continuous-infusion fluorouracil and leucovorin as first-line treatment in metastatic colorectal cancer: a multicenter phase II trial. J Clin Oncol 20:2651–2657

    Article  CAS  PubMed  Google Scholar 

  8. Cormier Y, Eisenhauer E, Muldal A, Gregg R, Ayoub J, Goss G, Stewart D, Tarasoff P, Wong D (1994) Gemcitabine is an active new agent in previously untreated extensive small cell lung cancer (SCLC). A study of the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol 5:283–285

    CAS  PubMed  Google Scholar 

  9. Abratt RP, Bezwoda WR, Falkson G, Goedhals L, Hacking D, Rugg TA (1994) Efficacy and safety profile of gemcitabine in non-small-cell lung cancer: a phase II study. J Clin Oncol 12:1535–1540

    CAS  PubMed  Google Scholar 

  10. Anderson H, Lund B, Bach F, Thatcher N, Walling J, Hansen HH (1994) Single-agent activity of weekly gemcitabine in advanced non-small-cell lung cancer: a phase II study. J Clin Oncol 12:1821–1826

    CAS  PubMed  Google Scholar 

  11. Guchelaar HJ, Richel DJ, van Knapen A (1996) Clinical, toxicological and pharmacological aspects of gemcitabine. Cancer Treat Rev 22:15–31

    CAS  PubMed  Google Scholar 

  12. Peters GJ, Bergman AM, Ruiz van Haperen VW, Veerman G, Kuiper CM, Braakhuis BJ (1995) Interaction between cisplatin and gemcitabine in vitro and in vivo. Semin Oncol 22 [4 Suppl 11]:72–79

  13. Kanzawa F, Saijo N (1997) In vitro interaction between gemcitabine and other anticancer drugs using a novel three-dimensional model. Semin Oncol 24 [2 Suppl 7]:S8–S16

  14. Bergman AM, Ruiz van Haperen VW, Veerman G, Kuiper CM, Peters GJ (1996) Synergistic interaction between cisplatin and gemcitabine in vitro. Clin Cancer Res 2:521–530

    CAS  PubMed  Google Scholar 

  15. Edelman MJ, Quam H, Mullins B (2001) Interactions of gemcitabine, carboplatin and paclitaxel in molecularly defined non-small-cell lung cancer cell lines. Cancer Chemother Pharmacol 48:141–144

    Article  CAS  PubMed  Google Scholar 

  16. Baldini E, Ardizzoni A, Prochilo T, Cafferata MA, Boni L, Tibaldi C, Neumaier C, Conte PF, Rosso R; Italian Lung Cancer Task Force (2001) Gemcitabine, Ifosfamide and Navelbine (GIN): activity and safety of a non-platinum-based triplet in advanced non-small-cell lung cancer (NSCLC). Br J Cancer 85:1452–1455

    Google Scholar 

  17. Frasci G, D'Aiuto G, Comella P, Thomas R, Capasso I, Botti G, Cortino GR, Di Bonito M, Rubulotta R, Vallone P, Comella G (2002) A phase I-II study on a gemcitabine-cyclophosphamide-fluorouracil/folinic acid triplet combination in anthracycline- and taxane-refractory breast cancer patients. Oncology 62:25–32

    Article  CAS  PubMed  Google Scholar 

  18. Comella P, Frasci G, Panza N, Manzione L, De Cataldis G, Cioffi R, Maiorino L, Micillo E, Lorusso V, Di Rienzo G, Filippelli G, Lamberti A, Natale M, Bilancia D, Nicolella G, Di Nota A, Comella G (2000) Randomized trial comparing cisplatin, gemcitabine, and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group. J Clin Oncol 18:1451–1457

    CAS  PubMed  Google Scholar 

  19. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41

    CAS  PubMed  Google Scholar 

  20. 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 7:1748–1756

    CAS  PubMed  Google Scholar 

  21. Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214

    PubMed  Google Scholar 

  22. Hainsworth JD, Burris HA 3rd, Erland JB, Morrissey LH, Meluch AA, Kalman LA, Hon JK, Scullin DC Jr, Smith SW, Greco FA (1999) Phase I/II trial of paclitaxel by 1-hour infusion, carboplatin, and gemcitabine in the treatment of patients with advanced nonsmall cell lung carcinoma. Cancer 85:1269–1276

    Article  CAS  PubMed  Google Scholar 

  23. Kelly K, Mikhaeel-Kamel N, Pan Z, Murphy J, Prindiville S, Bunn PA Jr (2000) A phase I/II trial of paclitaxel, carboplatin, and gemcitabine in untreated patients with advanced non-small cell lung cancer. Clin Cancer Res 6:3474–3479

    CAS  PubMed  Google Scholar 

  24. Greco FA, Hainsworth JD, Yardley DA, Burris HA III, Erland JB, Rodriguez GI, Shaffer DW (2002) Sequential paclitaxel/carboplatin/etoposide (PCE) followed by irinotecan/gemcitabine for patients (pts) with carcinoma of unknown primary site (CUP): a Minnie Pearl Cancer Research Network phase II trial (abstract 642). Proceedings of the Annual Meeting of the American Society of Clinical Oncology

  25. Vaishampayan U, Smith D, Redman B, Kucuk O, Ensley J, Hussain M (1999) Phase II evaluation of carboplatin, paclitaxel and gemcitabine in advanced urothelial carcinoma (abstract). Proceedings of the Annual Meeting of the American Society of Clinical Oncology

  26. Favaretto A, Paccagnella A, Oniga F, Tumolo S, Barbieri F, Ceresoli G, Gulisano M, Schiavon S (2000) Paclitaxel and carboplatin in combination with gemcitabine (PCG): a phase I-II trial in non-small cell lung cancer (NSCLC) (abstract 2003). Proceedings of the Annual Meeting of the American Society of Clinical Oncology

  27. Paccagnella A, Favaretto A, Bearz A Frustaci S, Barbieri F, Oniga F, Ghi MG, Biason R, Clerici MP, Ceresoli G, Chella A, Riccardi A (2002) Carboplatin/paclitaxel (CP) vs carboplatin/paclitaxel/gemcitabine (CPG) in advanced NSCLC: a phase II-III multicentric study (abstract 1349). Proceedings of the Annual Meeting of the American Society of Clinical Oncology

  28. Rosell R, Tonato M, Sandler A (1998) The activity of gemcitabine plus cisplatin in randomized trials in untreated patients with advanced non-small cell lung cancer. Semin Oncol 25 [4 Suppl 9]:27–34

    Google Scholar 

  29. Langer CJ, Gandara DR, Calvert P, Edelman MJ, Ozols RF (1999) Gemcitabine and carboplatin in combination: an update of phase I and phase II studies in non-small cell lung cancer. Semin Oncol 26 [1 Suppl 4]:12–18

    Google Scholar 

  30. Berlin JD, Alberti DB, Arzoomanian RZ, Feierabend CA, Simon KJ, Binger KA, Marnocha RM, Wilding G (1998–99) A phase I study of gemcitabine, 5-fluorouracil and leucovorin in patients with advanced, recurrent, and/or metastatic solid tumors. Invest New Drugs 16:325–330

    Article  CAS  PubMed  Google Scholar 

  31. Poplin E, Roberts J, Tombs M, Grant S, Rubin E (1999) Leucovorin, 5-fluorouracil, and gemcitabine: a phase I study. Invest New Drugs 17:57–62

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

    Keith T. Flaherty, James P. Stevenson, Stephen M. Hahn, Maryann Redlinger & Peter J. O'Dwyer

  2. Abramson Cancer Center, University of Pennsylvania, Medical Arts Building, Suite 103, 39th & Market Streets, Philadelphia, PA 19104, USA

    Keith T. Flaherty

Authors
  1. Keith T. Flaherty
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James P. Stevenson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephen M. Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maryann Redlinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter J. O'Dwyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This trial was supported with a grant from Eli Lilly and Company, Indianapolis, Indiana.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Flaherty, K.T., Stevenson, J.P., Hahn, S.M. et al. Phase I combination trial of gemcitabine, paclitaxel, and carboplatin in patients with advanced malignancy. Cancer Chemother Pharmacol 52, 217–222 (2003). https://doi.org/10.1007/s00280-003-0640-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-003-0640-x

Keywords

Search

Navigation