Abstract
Purpose
Combination chemotherapy regimens can improve survival in patients with advanced gastric and oesophageal adenocarcinoma. Docosahexaenoic acid (DHA)-paclitaxel is a novel conjugate formed by the covalent linkage of the fatty acid DHA to paclitaxel and may result in increased tumour exposure to paclitaxel without increased toxicity.
Patients and methods
In this single arm, phase II study of DHA-paclitaxel, eligible patients with previously untreated, inoperable locally advanced or metastatic adenocarcinoma of the oesophagus, oesophago-gastric junction or stomach were treated with DHA-paclitaxel (1,100 mg/m2) administered by 2-h intravenous infusion every 21 days.
Results
Fifty-four patients were recruited of whom 53 were evaluable for toxicity, and 48 for response. There were five confirmed partial responses (9.4%) by the RECIST criteria. The median duration of response was 87 days (range 49–97 days), the median time to progression was 84 days (95% CI 78–124 days), and median overall survival was 262 days (95% CI 205–357 days). Grade ≥3 neutropaenia occurred in 93% of patients, and febrile neutropaenia in 17% of patients.
Conclusions
DHA-paclitaxel has modest activity in patients with oesophago-gastric cancer and with haematological toxicity that is comparable to paclitaxel and docetaxel.
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References
Allum WH, Powell DJ, McConkey CC, Fielding JW (1989) Gastric cancer—a 25-year review. Br J Surg 76:535–540
Medical Research Council Oesophageal Working Party (2002) Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomized controlled trial. Lancet 359:1727–1733
Murad AM, Santiago FF, Petroianu A, et al (1993) Modified therapy with 5-fluorouracil, doxorubicin and methotrexate in advanced gastric cancer. Cancer 72:37–41
Glimelius B, Hoffman K, Haglund U, et al (1994) Initial or delayed chemotherapy with best supportive care in advanced gastric cancer. Ann Oncol 5:189–190
Pyrhonen S, Kuitonen T, Nyandoto P, Kouri M (1995) Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer 71:587–591
Findlay M, Cunningham D, Norman A, et al (1994) A phase II study in advanced gastro-oesophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol 5:609–616
Webb A, Cunningham D, Scarffe JH, et al (1997) Randomised trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15:261–267
Schoffski P (2002) New drugs for treatment of gastric cancer. Ann Oncol 13(Suppl 4):13–22
Polee MB, Hop WC, Kok TC (2003) Prognostic factors for survival in patients with advanced oesophageal cancer treated with cisplatin-based combination chemotherapy. Br J Cancer 89:2045–2050
Sauer LA, Stayman JW III, Dauchy RT (1982) Amino acid, glucose, and lactic acid utilization in vivo by rat tumors. Cancer Res 42:4090–4097
Sauer LA, Dauchy RT (1990) Tumour-host metabolic inter-relationships. Biochem Soc Trans 18:80–82
Sauer LA, Dauchy RT (1992) Uptake of plasma lipids by tissue-isolated hepatomas 7288CTC and 7777 in vivo. Br J Cancer 66:290–296
Bradley MO, Webb NL, Anthony FH, et al (2001) Tumor targeting by covalent conjugation of a natural fatty acid to paclitaxel. Clin Cancer Res 7:3229–3238
Wolff AC, Donehower RC, Carducci MK, et al (2003) Phase I study of docosahexaenoic acid-paclitaxel: a fatty acid conjugate with a unique pharmacology and toxicity profile. Clin Cancer Res 9:3589–3597
Therasse P, Arbuck SG, Eisenhauer EA, et al (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216
Kaplan EL, Meier P, et al (1958) Non-parametric estimation from incomplete observation. J Am Stat Assoc 53:457–481
Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10
Ajani JA, Fairweather J, Dumas P, et al (1998) Phase II trial of taxol in patients with advanced gastric carcinoma. Cancer J Sci Am 4:269–274
Kelsen D, Ajani J, Ilson D, et al (1994) A phase II trial of paclitaxel (taxol) in advanced esophageal cancer: preliminary report. Sem Oncol 21(5 Suppl 8):40–48
Ajani JA, Ilson DH, Daugherty K, et al (1994) Activity of taxol in patients with squamous cell carcinoma and adenocarcinoma of the esophagus. J Natl Cancer Inst 86:1086–1091
Mavroudis D, Kourousis C, Androulakis N, et al (2000) Frontline treatment of advanced gastric cancer with docetaxel and granulocyte colony-stimulating factor (G-CSF): a phase II trial. Am J Clin Oncol 23:341–344
Ajani JA, Ilson DH, Daugherty K, Kelsen DP (1995) Paclitaxel in the treatment of cancer of the oesophagus. Sem Oncol 22(Suppl 6):35–40
Einzig AI, Neuberg D, Remick SC, et al (1996) Phase II trial of docetaxel (Taxotere) in patients with adenocarcinoma of the upper gastrointestinal tract previously untreated with cytotoxic chemotherapy: the Eastern Cooperative Oncology Group (ECOG) results of protocol E1293. Med Oncol 13:87–93
Sulkes A, Smyth J, Sessa C, et al (1994) Docetaxel (Taxotere) in advanced gastric cancer: results of a phase II clinical trial. EORTC Early Clinical Trials Group. Br J Cancer 70:380–383
Ohtsu A, Boku N, Tamura F, et al (1998) An early phase II study of a 3-h infusion of paclitaxel for advanced gastric cancer. Am J Clin Oncol 21:416–419
Cascinu S, Graziano F, Cardarelli N, et al (1998) Phase II study of paclitaxel in pretreated advanced gastric cancer. Anti-Cancer Drugs 9:301–310
Moiseyenko VM, Ajani J, Tjulandin SA, et al (2005) Final results of a randomized controlled phase III trial (TAX 325) comparing docetaxel (T) combined with cisplatin (C) and 5-fluorouracil (F) to CF in patients (pts) with metastatic gastric adenocarcinoma (MGCI). J Clin Oncol 23(16S):3085
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The authors are grateful to all the study staff at each of the participating centres for their support of this study.
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Jones, R.J., Hawkins, R.E., Eatock, M.M. et al. A phase II open-label study of DHA-paclitaxel (Taxoprexin) by 2-h intravenous infusion in previously untreated patients with locally advanced or metastatic gastric or oesophageal adenocarcinoma. Cancer Chemother Pharmacol 61, 435–441 (2008). https://doi.org/10.1007/s00280-007-0486-8
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DOI: https://doi.org/10.1007/s00280-007-0486-8