Top

Published in:

01-02-2005 | Original Article

Phase II study of a fixed dose-rate infusion of gemcitabine associated with docetaxel in advanced non-small-cell lung carcinoma

Authors: J. De Castro, A. Lorenzo, S. Morales, J. Belón, J. Dorta, J. Lizón, C. Madroñal, P. M. Gallurt, E. Casado, J. Feliu, M. González Barón, Oncopaz Cooperative Group

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2005

Abstract

Purpose

To evaluate the efficacy and toxicity profile of the combination of docetaxel and prolonged gemcitabine infusion in front-line chemonaive patients with advanced non-small-cell lung cancer (NSCLC).

Patients and methods

A total of 50 chemonaive patients diagnosed with advanced NSCLC according to the AJCC/TNM classification system were included in the present study. Treatment consisted of 1000 mg/m² gemcitabine given as a 100-min continuous infusion (10 mg/m² per min) on days 1 and 8 of each course and 75 mg/m² docetaxel as a 60-min infusion on day 8, repeating each course every 21 days.

Results

The ECOG performance status of the patients were as follows: 0 (10%), 1 (60%), and 2 (30%). All patients had two-dimensionally measurable disease. Their median age was 63 years (range 41–75 years). Of the 50 patients, 28 (56%) had squamous cell carcinoma, 14 adenocarcinoma (28%), and 8 (16%) large-cell carcinoma, and 40% and 60% of patients presented with stage IIIB and IV disease, respectively. Of those with stage IV disease, 33% had more than one metastatic site. A total of 220 courses were administered with a median of five courses per patient. Of 46 patients assessed for response, 12 (26%) had a partial remission (95% CI 13–39%). In 19 patients (41%) the disease remained stable, while disease progression was observed in 15 (33%). The median time to disease progression was 4 months, and median survival time was 7 months. At 1 year, 25% of patients remained alive, and the main grade 3/4 toxicity (according to the WHO scale) consisted of neutropenia (n=6, 12%), asthenia (n=4, 8%), peripheral edema (n=3, 6%), dyspnea (n=3, 6%), and diarrhea (n=2, 4%).

Conclusions

Prolonged gemcitabine infusion combined with docetaxel is well tolerated and its efficacy is similar to that of other chemotherapeutic schemes used for NSCLC treatment. However, the prolonged infusion of gemcitabine did not appear to result in any improvement in outcome or toxicity versus the standard dose rate.

Marino P, Pampallona S, Preatoni A, Cantoni A, Invernizzi F (1994) Chemotherapy vs. supportive care in advanced non-small-cell lung cancer. Results of a meta-analysis of the literature. Chest 106:861–865PubMed

Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, et al (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 18:122–130PubMed

Wozniak AJ, Crowley JJ, Balcerzak SP, Weiss GR, Spiridonidis CH, Baker LH, et al (1998) Randomized trial comparing cisplatin with cisplatin plus navelbine in the treatment of advanced non-small cell lung cancer: a Southwest Oncology Group study. J Clin Oncol 16:2459–2465PubMed

Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, Jiroutek M, Johnson D (2000) Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol 18:623–631PubMed

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

Cerny T, Kaplan S, Pavlidis N, Schöffski P, Epelbaum R, Van Meerbeek J, et al (1994) Taxotere is an active drug in non small cell lung cancer: a phase II trial of the EORTC Early Clinical Trials Group (ECTG). Br J Cancer 70:384–387PubMed

Francis PA, Rigas JR, Kris MG, Pisters KMW, Orazem JP, Wooley KJ, et al (1994) Phase II trial of docetaxel in patients with stage III and IV non-small-cell lung cancer. J Clin Oncol 12:1232–1237PubMed

Zalcberg J, Millward M, Bishop J, Mckeage M, Zimet A, Toner G, et al (1998) Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer. J Clin Oncol 16:1948–1953PubMed

Fossella FV, Lee JS, Murphy WK, Lippman SM, Calayag M, Pang A, et al (1994) Phase II study of docetaxel for recurrent or metastatic non-small-cell lung cancer. J Clin Oncol 12:1238–1244PubMed

10.

Fossella FV, De Vore R, Kerr RN, Crawford J, Natale RR, Dunphy F, et al (2000) Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small cell lung cancer previously treated with platinum-containing chemotherapy regimens. J Clin Oncol 18:2354–2362PubMed

11.

Anderson H, Hopwood P, Stephens RJ, Thatcher N, Cottier B, Nicholson M, et al (2000) Gemcitabine plus best supportive care (BSC) vs. BSC in inoperable non-small cell lung cancer—a randomized trial with quality of life as the primary outcome. UKNSCLC Gemcitabine Group. Br J Cancer 83:447–453CrossRefPubMed

12.

Abbruzzese JL, Grunewald R, Weeks EA, Gravel D, Adams T, Nowak B, Mineishi S, Tarassoff P, Satterlee W, Raber MN, et al (1991) A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. J Clin Oncol 9:491–498PubMed

13.

Grunewald R, Abbruzzese JL, Tarassoff P, Plunkett W (1991) Saturation of 2′,2′-difluorodeoxycytidine 5′-triphosphate accumulation by mononuclear cells during a phase I trial of gemcitabine. Cancer Chemother Pharmacol 27:258–262PubMed

14.

Mountain CF (1997) Revisions in the international system for staging lung cancer. Chest 111:1710–1717PubMed

15.

World Health Organization (1979) WHO handbook for reporting results of cancer treatment. WHO offset publication no. 48. WHO, Geneva

16.

Zoli W, Ricotti L, Dal Susino M, Barzanti F, Frassinetti GL, Folli S, et al (1999) Docetaxel and gemcitabine activity in NSCLC cell lines and in primary cultures from human lung cancer. Br J Cancer 81:609–615CrossRefPubMed

17.

Ventriglia M, Estevez R, Alume H, et al (1998) Docetaxel (Taxotere) plus gemcitabine (Gemtro). A new combination in the treatment of patients with advanced non-small cell lung cancer (abstract 365). A preliminary analysis. Ann Oncol 9:96

18.

Georgoulias V, Kouroussis C, Androulakis N, Kakolyris S, Dimopoulos MA, Papadakis E, et al (1999) Front-line treatment of advanced non-small-cell lung cancer with docetaxel and gemcitabine: a multicenter phase II trial. J Clin Oncol 17:914–920PubMed

19.

Rubio G, Blajman C, Capó A, Cazap E, Chacón R, Freue M, et al (1999) Docetaxel and gemcitabine in metastatic non-small-cell lung cancer (NSCLC). A phase II study. Preliminary feasibility report. Proc Am Soc Clin Oncol 19:2012a

20.

Hejna M, Kornek GV, Raderer M, Ulrich-Pur H, Fiebiger WC, Marosi L, et al (2000) Treatment of patients with advanced nonsmall cell lung carcinoma using docetaxel and gemcitabine plus granulocyte-colony stimulating factor. Cancer 89:516–522CrossRefPubMed

21.

Rebattu P, Quantin X, Ardiet C, Morere JF, Azarian MR, Schuller-Lebeau MP, Pujol JL (2001) Dose-finding, pharmacokinetic and phase II study of docetaxel in combination with gemcitabine in patients with inoperable non-small cell lung cancer. Lung Cancer 33:277–287CrossRefPubMed

22.

Popa IE, Stewart K, Smith FP, Rizvi NA (2002) A phase II trial gemcitabine and docetaxel in patients with chemotherapy-naive, advanced nonsmall cell lung carcinoma. Cancer 95:1714–1719CrossRefPubMed

23.

Kwan P, Mukhopadhyay P, Rastogi A, Osman MR (2000) A novel administration of gemcitabine (via constant dose rate) in combination with docetaxel in advanced non-small cell lung cancer (abstract 1985). Proc Am Soc Clin Oncol 19:507a

24.

Galetta D, Gebbia V, Giotta F, Durini E, Romito S, Borsellino N, Cazzato C, Pezzella G, Colucci G (2002) Gemcitabine and docetaxel every 2 weeks in advanced non-small cell lung cancer: a phase II study of the Gruppo Oncologico Italia Meridionale. Lung Cancer 38:79–84CrossRefPubMed

25.

Huang P, Chubb S, Hertel LW, Grindey GB, Plunkett W (1991) Action of 2′,2′-difluorodeoxycytidine on DNA synthesis. Cancer Res 51:6110–6117PubMed

26.

Baker CH, Banzon J, Bollinger JM, Stubbe J, Samano V, Robins MJ, et al (1991) 2′-Deoxy-2′-methylenecytidine and 2′-deoxy-2′,2′-difluorodeoxycytidine 5′-diphosphates: potent mechanism-based inhibitors of ribonucleotide reductase. J Med Chem 34:1879–1884PubMed

27.

28.

Touroutoglou N, Gravel D, Raber MN, Plunkett W, Abbruzzese JL (1998) Clinical results of a pharmacodynamically-based strategy for higher dosing of gemcitabine in patients with solid tumors. Ann Oncol 9:1003–1008CrossRefPubMed

29.

Grunewald R, Kantarjian H, Du M, Faucher K, Tarassoff P, Plunkett W (1992) Gemcitabine in leukemia: a phase I clinical, plasma and cellular pharmacology study. J Clin Oncol 10:406–413PubMed

30.

Georgoulias V, Papadakis E, Alexopoulos A, Tsiafaki X, Rapti A, Veslemes M, et al (2001) Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial. Lancet 357:1478–1484CrossRefPubMed

31.

Tibaldi C, Russo F, Bernardini I, Chella A, Ricchi A, Michelotti A, Falcone A (2003) Prolonged gemcitabine infusion after gemcitabine 30-minutes infusion alone or in combination with cisplatin in advanced NSCLC. Proc Am Soc Clin Oncol 22:2789a

32.

Caffo O, Santo A, Binato S, Zaffaroni M, Zucchetti M, Centonze M, et al (2003) A dose-finding and pharmacokinetic study of gemcitabine in prolonged infusion in combination with cisplatin in advanced non-small cell lung cancer patients. Proc Am Soc Clin Oncol 22:2747a

33.

Capuzzo F, Scagliotti G, Novello S, Selvaggi G, De Marinis F, Martelli O, et al (2003) A parallel randomized phase II trial evaluating standard versus prolonged infusion gemcitabine as front-line treatments in advanced non-small cell lung cancer. Proc Am Soc Clin Oncol 22:2634a

34.

Kosmas C, Tsavaris N, Vadiaka M, Stavroyianni N, Koutras A, Malamos N, Onyenadum A, Rokana S, Polyzos A, Kalofonos HP (2001) Gemcitabine and docetaxel as second-line chemotherapy for patients with nonsmall cell lung carcinoma who fail prior paclitaxel plus platinum-based regimens. Cancer 92:2902–2910CrossRefPubMed

Title: Phase II study of a fixed dose-rate infusion of gemcitabine associated with docetaxel in advanced non-small-cell lung carcinoma
Authors: J. De Castro
A. Lorenzo
S. Morales
J. Belón
J. Dorta
J. Lizón
C. Madroñal
P. M. Gallurt
E. Casado
J. Feliu
M. González Barón
Oncopaz Cooperative Group
Publication date: 01-02-2005
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 2/2005
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-004-0869-z

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Patients and methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2005

Plasma pharmacokinetics and tissue distribution of the breast cancer resistance protein (BCRP/ABCG2) inhibitor fumitremorgin C in SCID mice bearing T8 tumors

Investigations in vivo of the effects of carbogen breathing on 5-fluorouracil pharmacokinetics and physiology of solid rodent tumours

Tissue distribution of arsenic species in rabbits after single and multiple parenteral administration of arsenic trioxide: tissue accumulation and the reversibility after washout are tissue-selective

Absorption and metabolism of genistein and its five isoflavone analogs in the human intestinal Caco-2 model

Lack of strain-related differences in drug metabolism and efflux transporter characteristics between CD-1 and athymic nude mice

Reversal of multidrug resistance of cancer through inhibition of P-glycoprotein by 5-bromotetrandrine

Keynote webinar | Spotlight on antibody–drug conjugates in cancer