Paclitaxel esophageal cancer

Within the multiple subsites of this tumor grouping, most work has been done in esophageal cancer. The large majority of these patients have been treated with paclitaxel in combination with radiation (Table 3). The experience with docetaxel is essentially limited to patients treated on phase I trials for thoracic malignancies that used radiation in combination with docetaxel (68,111). The situation is much the same for both pancreatic and gastric cancers as well. The rationale for looking at combination therapy that incorporates paclitaxel is much the same as in other disease sites, i.e., its activity in systemic disease (112), its potent preclinical radiosensitizing properties (38), and evidence from randomized trials that there is a benefit to combined modality therapy that includes at least radiation and chemotherapy (113-116). 

Blanke CD, Choy H, Teng M, et al. Concurrent paclitaxel and thoracic irradiation for locally advanced esophageal cancer. Semin Radiat Oncol 1999 9(2 Suppl l) 43-52. 

Wright CD, Wain JC, Lynch TJ, et al. Induction therapy for esophageal cancer with paclitaxel and hyperfractionatedradiotherapy aphaselandllstudy. JThorac CardiovascSurg 1997 114(5) 811—815. 

Safran H, Gaissert H, Akerman P, et al. Paclitaxel, cisplatin, and concurrent radiation for esophageal cancer. Cancer Invest 2001 19(1) 1—7. 

Meluch AA, Hainsworth JD, Gray JR, et al. Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged infusion 5-fluorouracil, and radiation therapy in localized esophageal cancer preliminary results of a Minnie Pearl Cancer Research Network phase II trial. Cancer J Sci Am 1999 5 (2) 84-91. 

Adelstein DJ, Rice TW, Rybicki LA, et al. Does paclitaxel improve the chemoradiotherapy of locoregionally advanced esophageal cancer A nonrandomized comparison with fluorouracil-based therapy. J Clin Oncol 2000 18(10) 2032-2039. 

Phase II studies of paclitaxel, infused as a single agent over 24 h every 3 wk, showed promising results for patients with metastatic or locally unresectable esophageal cancer. The overall response rate was 32%, with a median survival of 13.2 mo (53). 

Table 7 summarizes selected phase Eli studies of paclitaxel/radiation in esophageal cancer. Although pathologic complete response rates have been encouraging, ranging from 11 41 %, these regimens have not been tested in a randomized fashion against the more standard cisplatin, 5-FU based therapies. 

Vanderbilt University Medical Center has recently completed accruing patients to a Phase II study of neoadjuvant chemoradiation, which consists of preoperative paclitaxel (175 mg/m2,3-h infusion) followed by cisplatin 75 mg/m2 d 1 and 21. Concurrent radiation was given to a total dose of 3000 cGy, in 200 cGy/fraction. Patients who are resectable go on to surgery 4 wk after completion of chemoradiation, whereas those who are unresectable (i.e., cervical esophageal cancer) continue to a total dose of 60 Gy without treatment interruptions. One month following surgery, patients receive two cycles (q 21-28 d) of postoperative chemotherapy, which consists of paclitaxel 175 mg/m2 over 3 h d 1,5-FU 350 mg/m2, d 1-3, and leucovorin 300 mg d 1-3. Preliminary analysis of this... 

Blanke CD, Chiappori A, Epstein B, et al. A Phase II Trial of Neoadjuvant Paclitaxel (T) and Cisplatin (P) with Radiotherapy, Followed by Surgery (S) and Postoperativve T with 5-Fluorouracil (F) and Leucovorin (L) in Patients (pts) with Locally Advanced Esophageal Cancer (LAEC). ProcAnnu Meet Am Soc Clin Oncol 1997 16 A1006. 

Meluch A, Greco F, Burris H m, et al. Preoperative Paclitaxel, Carbonplatin, 5-FU and Radiation Therapy for Localized Esophageal Cancer. Proc Annu Meet Am Soc Clin Oncol 2001 20 A636. 

Ku, G.Y., flson, D.H., Schwartz, L.H., Capanu, M., O Reilly, E., Shah, M.A., Kelsen, D.P., and Schwartz, G.K. (2008) Phase II trial of sequential paclitaxel and Ih infusion of bryostatin-1 in patients with advanced esophageal cancer. Cancer Chemother. Pharmacol., 62, 875-880. 

It is well established that systemic administration of paclitaxel inaeases the efficacy of chemo radiotherapy, thus the lack of significant improvement shown by this combined study was attributed to the localized delivery of paclitaxel in the form of an OncogeF. Since OncogeF failed to show a significant improvement in the efficacy, it was terminated as a potential therapy for esophageal cancer in 2010 [25]. 

Paclitaxel (Taxol) -Ovarian cancer breast cancer KS NSCLC SCLC esophageal and head and neck cancers testicular cancer bladder cancer cervical and endometrial cancers... 

The first compound of the taxanes series, paclitaxel (Taxol), was isolated from the bark of the Western yew tree in 1971. It and its congenic, the semisynthetic docetaxel (Taxotere), exhibit unique pharmacological actions as inhibitors of mitosis, differing from the vinca alkaloids and colchicine derivatives in that they bind to a different site on P-tubulin and promote rather than inhibit microtubule formation. The drugs have a central role in the therapy of ovarian, breast, lung, esophageal, bladder, and head and neck cancers. 

Cisplatin, in combination with bleomycin, etoposide, ifosfamide, or vinblastine, cures 90% of patients with testicular cancer. Used with paclitaxel, cisplatin induces complete response in most patients with carcinoma of the ovary. Cisplatin produces responses in cancers of the bladder, head and neck, cervix, and endometrium all forms of carcinoma of the lung anal and rectal carcinomas and neoplasms of childhood. The drug sensitizes cells to radiation therapy and enhances control of locally advanced lung, esophageal, and head and neck tumors when given with irradiation. 

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