Primary chemotherapy with gemcitabine, liposomal doxorubicin and docetaxel in patients with locally advanced breast cancer: Results of a phase I trial

Anti-Cancer Drugs

Volumn 16, Issue 1, 2005, Pages 21-29

  Schmid, Peter ^a   Krocker, Jutta ^b   Schulz, Carsten Oliver ^a   Michniewicz, Katarzyna ^b   Dieing, Annette ^a   Eggemann, Holm ^b   Heilmann, Volker ^c   Blohmer, Jens Uwe ^a   Sezer, Orhan ^a   Elling, Dirk ^b   Possinger, Kurt ^a  

^a HUMBOLDT UNIVERSITY   (Germany)

^b Oskar Ziethen Hospital   (Germany)

^c UNIVERSITY HOSPITAL ULM   (Germany)

Author keywords

Docetaxel; Gemcitabine; Liposomal doxorubicin; Locally advanced breast cancer; Neoadjuvant; Primary chemotherapy

Indexed keywords

ANTIEMETIC AGENT; DEXAMETHASONE; DOCETAXEL; DOXORUBICIN; GEMCITABINE; GRANULOCYTE COLONY STIMULATING FACTOR;

ADULT; ADVANCED CANCER; AGED; ALOPECIA; ANEMIA; ARTICLE; BLOOD TOXICITY; BONE MARROW SUPPRESSION; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER REGRESSION; CANCER STAGING; CLINICAL ARTICLE; CLINICAL TRIAL; COLITIS; CONSTIPATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DOSE RESPONSE; DOSE TIME EFFECT RELATION; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG SAFETY; FEBRILE NEUTROPENIA; GASTROINTESTINAL TOXICITY; HUMAN; INFECTION; LIVER TOXICITY; MAXIMUM TOLERATED DOSE; MUCOSA INFLAMMATION; NAUSEA; OPEN STUDY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RASH; STOMATITIS; THROMBOCYTOPENIA; VOMITING;

ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BREAST NEOPLASMS; CARCINOMA, DUCTAL, BREAST; CARCINOMA, LOBULAR; DEOXYCYTIDINE; DOSE-RESPONSE RELATIONSHIP, DRUG; DOXORUBICIN; FEMALE; HUMANS; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOADJUVANT THERAPY; NEOPLASM STAGING; TAXOIDS; TREATMENT OUTCOME;

EID: 19944432156     PISSN: 09594973     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001813-200501000-00003     Document Type: Article

References (40)

1. Early Breast Cancer Trialists' Collaborative Group. Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer: an overview of 61 randomized trials among 28,896 women. N Engl J Med 1998; 319:1681-1692.
2. Early Breast Cancer Trialists' Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 1998; 352:930-942.
3. Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 1997; 15: 2483-2493.
4. Mauriac L, MacGrogan G, Avril A, Durand M, Floquet A, Debled M, et al. Neoadjuvant chemotherapy for operable breast carcinoma larger than 3cm: a unicentre randomized trial with a 124-month median follow-up. Institut Bergonie Bordeaux Groupe Sein (IBBGS). Ann Oncol 1999; 10:47-52.
5. van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol 2001; 19:4224-4237.
6. Broet P, Scholl SM, de la Rochefordiere A, Fourquet A, Moreau T, De Rycke Y, et al. Short- and long-term effects on survival in breast cancer patients treated by primary chemotherapy: an updated analysis of a randomized trial. Breast Cancer Res Treat 1999; 58:151-156.
7. Semiglazov VF, Topuzov EE, Bavli JL, Moiseyenko VM, Ivanova OA, Seleznev IK, et al. Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer. Ann Oncol 1994; 5:591-595.
8. Kuerer HM, Newman LA, Ames FC, Theriault RL, Hunt KK, Sneige N, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response (PCR) to doxorubicin based neoadjuvant chemotherapy. Proc Am Soc Clin Oncol 1998; 17:abstr 451.
9. Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 1998; 16:2672-2685.
10. Cristofanili M, Fratarcangeli T, Frye D, Esteva F, Rosales M, Booser DJ, et al. Weekly high dose paclitaxel (HD-P) has significant antitumor activity in inflammatory breast cancer (IBC). Proc Am Soc Clin Oncol 2001; 20:15b (abstr 1807).
11. Estevez LG, Cuevas JM, Anton A, Florian J, Velasco A, Jiménez Diaz F, et al. Weekly docetaxel (D) in stage II and III breast cancer patients: an effective regimen as primary chemotherapy (PC), GEICAM study group. Proc Am Soc Clin Oncol 2001; 20:37b (abstr 1897).
12. Gradishar WJ. Docetaxel as neoadjuvant chemotherapy in patients with stage III breast cancer. Phase II study: preliminary results. Oncology 1997; 11(suppl 8):15-18.
13. Buzdar AU, Singletary SE, Theriault RL, Booser DJ, Valero V, Ibrahim N, et al. Prospective evaluation paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin and cyclophosphamide as neoadjuvant therapy in patient with operable breast cancer. J Clin Oncol 1999; 17:3412-3417.
14. Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, et al. Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 2002; 20:1456-1466.
15. Vinholes J, Bouzid K, Salas F. Preliminary results of a multicentre phase III trial of taxotere and doxorubicin (AT) versus 5-fluouracil, doxorubicin and cyclophosphamide (FAC) in patients (Pts) with unresectable locally advanced breast cancer (ULAB). Proc Am Soc Clin Oncol 2001; 20:abstr 101.
16. Luporsi E, Vanlemmens L, Coudert B. 6 cycles of FEC 100 vs 6 cycles of epirubicin-docetaxel (ED) as neoadjuvant chemotherapy in operable breast cancer patients (Pts): preliminary results of a randomized phase II trial of GIREC S01. Proc Am Soc Clin Oncol 2000; 19:abstr 355.
17. Evans TRJ, Gould A, Foster E, Crown JP, Leonard RCF, Mansi JL, et al. Phase III randomised trial of adriamycin and docetaxel (AD) versus adriamycin and cyclophosphamide (AC) as primary medical therapy (PMT) in women with breast cancer: an ACCOG study. Proc Am Soc Clin Oncol 2002; 21:abstr 136.
18. Conte PF, Bengala C, Danesi R, Baldini E, Donati S, Pazzagli I, et al. Gemcitabin, Epirubicin and Paclitaxel (GET) in metastastic breast cancer (MBC): preliminary report of a phase I/II study with pharmacokinetic and peripheral blood progenitor cell (PBPC) mobilization assessment. Proc Am Soc Clin Oncol 1998; 17:134a (A511)
19. Conte P, Bengala C, Donati S, Baldini E, Pazzagli I, Favre C, et al. Gemcitabin, Epirubicin and Taxol (GET) followed by High Dose Chemotherapy (HDCT): high activity with good tolerability in metastastic breast cancer patients. Proc Am Soc Clin Oncol 1999; 18:118a (A449).
20. Harris L, Batist G, Belt R, Rovira D, Navari R, Azarnia N, et at. Liposome-encapsulated doxorubicin compared with conventional doxorublcin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma. Cancer 2002; 94:25-36,
21. Batist G, Ramakrishnan G, Rao CS, Chandrasekharan A, Gutheil J, Guthrie T, et al. Reduced cardiotoxicity and preserved antilumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, mullicenler trial of metastalic breast cancer. J Clin Oncol 2001; 19: 1444-1454,
22. Heinemann V, Schulz L, Issels-RD, Plunkett W. Gemcitabine: a modulator of intracellular nucleotide and deoxynucleotide metabolism. Semin Oncol 1995; 22(suppl 11):11-18.
23. Plunkett W, Huang P, Xu YZ, Heinemann V, Grunewald R, Gandhi V. Gemcitabine: metabolism, mechanisms of action, and self-potentiation. Semin Oncol 1995; 22(suppl 11):3-10.
24. Huang P, Plunkett W. Induction of apoptosis by gemcitabine. Semin Oncol 1995; 22(suppl 11):19-25.
25. Grunewald R, Abbruzzese JL, Tarassoff P, Plunkett W. Saturation of 2′,2′-difluorodeoxycytidine 5′-triphosphate accumulation by mononuclear cells during a phase I trial of gemcitabine. Cancer Chemother Pharmacol 1991 27:258-262.
26. Abbruzzese JL, Grunewald R, Weeks EA. A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. J Clin Oncol 1991; 9: 491-498.
27. Veerman G. Ruiz van Haperen VW, Vermerken JB. Antitumor activity of prolonged as compared with bolus administration of 2′,2′- difluorodeoxycytidine in vivo against murine colon tumors. Cancer Chemother Pharmacol 1996; 38:335-342.
28. Maurel J, Zorrilla M, Puertolas T, Anton A, Herrero A, Artal A, et al. Phase I trial of weekly gemcitabine at 3-h infusion in refractory, heavily pretreated advanced solid tumors. Anticancer Drugs 2001; 12:713-717,
29. Schmid P, Fritz J, Schweigert M, Beinert T, Fenner M, Dieing A, et al. Prolonged infusion of gemcitabine in advanced solid tumors: a phase I study. Onkologie 2002; 25(suppl 4):53.
30. 2) levels. Invest New Drugs 1997; 15:115-121.
31. Akrivakis K, Schmid P, Rath B, Schweigert M, Sezer O. Mergenthaler HG, et al. Prolonged infusion of gemcitabine in stage IV breast cancer: a phase I study. Anticancer Drugs 1999; 10:525-531.
32. Brand R, Capadano M, Tempero M. A phase I trial of weekly gemcitabine administered as a prolonged infusion in patients with pancreatic cancer and other solid tumors. Invest New Drugs 1997; 15:331-341.
33. Touroutoglou N, Gravel D, Raber MN, Plunkett W, Abbruzzese JL. Clinical results of a pharmacodynamically-based strategy for higher dosing of gemcitabine in patients with solid tumors. Ann Oncol 1998; 9: 1003-1008.
34. Cascinu S, Frontini L, Labianca R, Catalano V. Barni S, Graiff C, et al. A combination of a fixed dose rate infusion of gemcitabine associated to a bolus-5-fluorouracil in advanced pancreatic cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). Ann Oncol 2000; 11:1309-1311.
35. Zoli W, Ricotti L, Barzanti F, Dal Susino M, Frassineti GL, Milandri C, et al. Schedule-dependent interaction of doxorubicin, paclitaxel and gemcitabine in human breast cancer cell lines, Int J Cancer 1999; 80: 413-416.
36. Zielinski C, Beslija S, Mrsic-Krmpotic Z, Jassem J, Wiltschke C, Kahan Z, et al. Gemcitabine/epirubicin/paclitaxel (GET) vs 5-fluorouracil/epirubicin/ cyclophosphamide (FEC) as first-line treatment in metastatic breast cancer (MBC): demographics of a randomized, multicenter phase III trial of the Central European Cooperative Oncology Group (CECOG). Proc Am Soc Clin Oncol 2003; 22:abstr 26.
37. Conte PF, Gennari A, Santoro A, Bottini A, Crino L, Tumolo S, et al. Induction chemotherapy in operable breast cancer: a multicenter Italian phase II study with the GET regimen. Proc Am Soc Clin Oncol 2003; 22:abstr 140.
38. Hamm J, Wilson J, Lembersky BC, Robidoux A, Raymond J, Kardinal C, et al. Neoadjuvant chemotherapy with gemcitabine (G), epirubicin (E), and paclitaxel (T) in locally advanced breast cancer (LABC): a phase II trial of the NSABP Foundation Research Group. Breast Cancer Res Treat 2003; 82(suppl 1):abstr 235.
39. Yardley DA, Whitworth P, Greco FA, Burris III HA, White M,Thomas M, et al. Neoadjuvant gemcitabine, epirubicin, and docetaxel (GET). Preliminary results from a multicenter phase II trial in inflammatory and locally advanced breast cancer. Breast Cancer Res Treat 2003; 82(suppl 1): abstr 237.
40. Schneeweiss A, Geberth M, Sinn H-P, Krauss K, Beldermann F, Wagner U, et al. The triplet gemcitabine, epirubicin, and docetaxel as primary systemic chemotherapy in primary breast cancer T2-4, NO-2, MO: final primary endpoint analysis of a multicentric phase I/II trial. Breast Cancer Res Treat 2003; 82(suppl 1):abstr 242.