Investigational New Drugs

, Volume 25, Issue 1, pp 57–62 | Cite as

Cisplatin plus gemcitabine on days 1 and 4 every 21 days for solid tumors: Result of a dose-intensity study

  • Hector Soto ParraEmail author
  • Raffaele Cavina
  • Fiorenza Latteri
  • Elisabetta Campagnoli
  • Emanuela Morenghi
  • Walter Torri
  • Giorgio Brambilla
  • Marco Alloisio
  • Armando Santoro


Background: Three and 4-week cisplatin-gemcitabine schedules have shown similar dose-intensity (DI) and activity in non-small-cell lung cancer (NSCLC). The 3-week schedule is generally preferred because it enables better treatment compliance. To improve DI and compliance further, we delivered gemcitabine plus cisplatin over 4 days every 21 days.

Methods: Patients with any stage NSCLC or epithelial neoplasms and an ECOG PS ≤2 were given gemcitabine 1000 mg/m2 on days 1 and 4 plus cisplatin 70 mg/m2 on day 2 of a 21-day cycle. Minimax design was used and a received DI for gemcitabine of ≥580 mg/m2/wk was considered successful.

Results: Thirty-nine patients (34 NSCLC, 5 epithelial neoplasias) were enrolled. SWOG grade 3–4 neutropenia and thrombocytopenia were observed in 17.9% and 12.8% of patients, respectively. Nonhematological toxicity was minimal. Twenty-eight (18%) of 158 cycles required dose modifications and/or delays. Twenty-five patients received a gemcitabine dose intensity of ≥580 mg/m2/wk. The received DIs were 601.8 mg/m2/wk for gemcitabine and 21.0 for cisplatin, with a relative DIs of 90.3% and 90.1%, respectively. The response rate of 27 evaluable patients with NSCLC was 44% (95% confidence interval [CI], 25.3 to 62.7%).

Conclusions: The shorter schedule of gemcitabine on days 1 and 4 plus cisplatin on day 2 produces an effective DI and a toxicity profile comparable to that of weekly regimens.


Cisplatin Dose-intensity Gemcitabine Non-small-cell lung cancer 


  1. 1.
    Abbruzzese JL, Grunewald R, Weeks EA, Gravel D, Adams, Nowak B, Mineishi S, Tarassoff P, Satterlee W, Raber MN (1991) A phase I clinical, plasma and cellular pharmacology study of gemcitabine. J Clin Oncol 9:491–498PubMedGoogle Scholar
  2. 2.
    Abratt RP, Bezwoda WR, Goedhals L, Hacking DJ (1997) Weekly gemcitabine with monthly cisplatin: Effective chemotherapy for advanced non-small-cell lung cancer. J Clin Oncol 15:744–749PubMedGoogle Scholar
  3. 3.
    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 12:1821–1826PubMedGoogle Scholar
  4. 4.
    Anton A, Diaz-Fernandez N, Gonzalez Larriba JL, Vadell C, Masutti B, Montalar J, Barneto I, Artal A, Rosell R (1998) Phase II trial assessing the combination of gemcitabine and cisplatin in advanced non-small cell lung cancer (NSCLC). Lung Cancer 22:139–148CrossRefPubMedGoogle Scholar
  5. 5.
    Cardenal F, Lopez-Cabrerizo MP, Anton A, Alberola V, Massuti B, Carrato A, Barneto I, Lomas M, Garcia M, Lianes P, Montalar J, Vadell C, Gonzalez-Larriba JL, Nguyen B, Artal A, Rosell R (1999) Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 17:12–18PubMedGoogle Scholar
  6. 6.
    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 18:1451–1457PubMedGoogle Scholar
  7. 7.
    Crinò L, Scagliotti G, Marangolo M, Figoli F, Clerici M, De Marinis F, Salvati F, Cruciani G, Dogliotti L, Pucci F, Paccagnella A, Adamo V, Altavilla G, Incoronato P, Trippetti M, Mosconi AM, Santucci A, Sorbolini S, Oliva C, Tonato M (1997) Cisplatin-gemcitabine combination in advanced non-small-cell lung cancer: a phase II study. J Clin Oncol 15:297–303PubMedGoogle Scholar
  8. 8.
    Crinò L, Scagliotti GV, Ricci S, De Marinis F, Rinaldi M, Gridelli C, Ceribelli A, Bianco R, Marangolo M, Di Costanzo F, Sassi M, Barni S, Ravaioli A, Adamo V, Portalone L, Cruciani G, Masotti A, Ferrara G, Gozzelino F, Tonato M (1999) Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: a randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol 17:3522–3530PubMedGoogle Scholar
  9. 9.
    Ellis PA, Smith IE, Hardy JR, Nicolson MC, Talbot DC, Ashley SE, Priest K (1995) Symptom relief with MVP (mitomycin, vinblastine and cisplatin) chemotherapy in advanced non-small cell lung cancer. Br J Cancer 71:366–370PubMedGoogle Scholar
  10. 10.
    Gatzemeier U, Shepherd FA, Le Chevalier T, Weynants P, Cottier B, Groen HJ, Rosso R, Mattson K, Cortes-Funes H, Tonato M, Burkes RL, Gottfried M, Voi M (1996) Activity of gemcitabine in patients with non-small cell lung cancer: a multicentre, extended phase II study. Eur J Cancer 32A:243–248CrossRefPubMedGoogle Scholar
  11. 11.
    Green S, Weiss GR (1992) Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs 10:239–253CrossRefPubMedGoogle Scholar
  12. 12.
    Hryniuk W (1988) The importance of dose intensity in outcome of chemotherapy. In: Hellman S, De Vita V, Rosenberg S (eds) Important Advanced in Oncology. Lippincott Philadelphia PA, pp. 121–141Google Scholar
  13. 13.
    Non-small Cell Lung Cancer Collaborative group Chemotherapy in non-small cell lung cancer (1995) A meta-analysis using updated data on individual patients from 52 randomized clinical trials—Non-small Cell Lung Cancer Collaborative Group. Br Med J 311:899–909Google Scholar
  14. 14.
    O’Rourke TJ, Brown TD, Havlin K, Kuhn JG, Craig JB, Burris HA, Satterlee WG, Tarassoff PG, Von Hoff DD (1994) Phase I clinical trial of gemcitabine given as an intravenous bolus on 5 consecutive days. Eur J Cancer 30A:417–418CrossRefPubMedGoogle Scholar
  15. 15.
    Pollera CF, Ceribelli A, Crecco M, Calabresi F (1994) Weekly gemcitabine in advanced or metastatic solid tumors. A clinical phase I study. Invest New Drugs 12:111–119CrossRefPubMedGoogle Scholar
  16. 16.
    Poplin EA, Corbett T, Flaherty L, Tarasoff P, Redman BG, Valdivieso M, Baker L (1992) Difluorodeoxycytidine (dFdC, gemcitabine): a phase I study. Invest New Drugs 10:165–170CrossRefPubMedGoogle Scholar
  17. 17.
    Rinaldi M, Crinò L, Scagliotti GV, Mosconi AM, De Marinis F, Gridelli C, Selvaggi G, Della Giulia M, Darwish S, Porrozzi S, Novello S, Cipri A, Bartolucci R, Calandri C, Tonato M (2000) A three-week schedule of gemcitabine-cisplatin in advanced non-small-cell lung cancer with two different cisplatin dose levels: a phase II randomized trial. Ann Oncol 10:1295–1300CrossRefGoogle Scholar
  18. 18.
    Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, Mattson K, Manegold C, Palmer MC, Gregor A, Nguyen B, Niyikiza C, Einhorn LH (2000) Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 18:122–130PubMedGoogle Scholar
  19. 19.
    Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH (2002) The Eastern Cooperative Oncology Group Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92–98CrossRefPubMedGoogle Scholar
  20. 20.
    Shepherd FA, Burkes RL, Cormier Y, Crump M, Feld R, Strack T, Schulz M (1996) Final results of the Canadian phase I dose escalation trial of gemcitabine and cisplatin for advanced non-small cell lung cancer. Semin Oncol 23:48–54PubMedGoogle Scholar
  21. 21.
    Simon R (1989) Optimal two-stage designs for phase II clinical trials. Controlled Clin Trials 10:1–10CrossRefPubMedGoogle Scholar
  22. 22.
    Soto Parra H, Cavina R, Latteri F, Sala A, Dambrosio M, Antonelli G, Morenghi E, Alloisio M, Ravasi G, Santoro A (2002) Three-week versus four-week schedule of cisplatin and gemcitabine: Results of a randomized phase II study. Ann Oncol 13:1080–1086CrossRefPubMedGoogle Scholar
  23. 23.
    WHO Handbook for reporting Results of Cancer Treatment (1979) Publication no. 48. World Health Organization, GenevaGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Hector Soto Parra
    • 1
    Email author
  • Raffaele Cavina
    • 1
  • Fiorenza Latteri
    • 1
  • Elisabetta Campagnoli
    • 1
  • Emanuela Morenghi
    • 2
  • Walter Torri
    • 3
  • Giorgio Brambilla
    • 4
  • Marco Alloisio
    • 5
  • Armando Santoro
    • 1
  1. 1.Department of Medical Oncology and HematologyIstituto Clinico HumanitasRozzanoItaly
  2. 2.Clinical Sperimentation OfficeIstituto Clinico HumanitasRozzanoItaly
  3. 3.Department of OncologyBiometry Unit, Istituto di Ricerca FarmacologicaRozzanoItaly
  4. 4.Division of Diagnostic RadiologyIstituto Clinico HumanitasRozzano56 Rozzano-MilanItaly
  5. 5.Division of Thoracic SurgeryIstituto Clinico HumanitasRozzanoItaly

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