Paclitaxel recurrent

A similar small phase II trial from Germany has reported on seven patients receiving concurrent chemoradiation for transitional cell carcinoma of the bladder with cisplatin and paclitaxel (96). The authors conclude that this combination is at least feasible given an acceptable acute toxicity profile and reasonable efficacy. Another small series is reported by Nichols et al. (97) where eight patients received radiation with concurrent paclitaxel and carboplatin in an attempt at bladder preservation. Three of the patients remain free of distant metastases, and local recurrence has occurred in three. 

Single-agent activity of paclitaxel was initially evaluated by the Eastern Cooperative Oncology Group (ECOG) in a select cohort of 34 patients with unresectable, recurrent, or metastatic disease (34). The overall response rate was 40% (4 CR, 8 PR). Myelosuppression was the primary toxicity. The median survival was 9.2 mo with a 1-yr survival of 33%. 

A randomized phase II trial comparing weekly methotrexate (MTX, 40-60 mg/m2) vs triweekly paclitaxel (175-225 mg/m2 by 3-h or 24-h infusion) in the recurrent or metastatic setting was prematurely closed as a result of toxicity and minimal response (76). 

The Eastern Cooperative Oncology Group has studied the combination of high-dose paclitaxel and cisplatin with G-CSF support in comparison to low-dose paclitaxel and cisplatin in a recent phase III trial (77). Patients with locally advanced, recurrent, or metastatic disease were randomly placed on arm A of paclitaxel (200 mg/m2 over a 24-h infusion), cisplatin (75 mg/m2), and G-CSF (starting d 3 until the ANC was >10,000/pL) or armB ofpaclitaxel (135 mg/m2 over a 24-h infusion) and cisplatin (75 mg/m2). The tre atment was repeated every 21 d until progression of disease or a total of 12 cycles. 

The RTOG has an ongoing phase II study analyzing the use of paclitaxel and cisplatin in combination with split-course concomitant radiotherapy in patients with recurrent squamous cell carcinoma requiring reirradiation. Cisplatin and paclitaxel are administered d 1-... 

Vermorken J, Catimel G, Mulder PD, et al. Randomized phase II trial of weekly methotrexate (MTX) versus two schedules of triweekly paclitaxel (taxol) in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). ProcAnnu Meet Am Soc Clin Oncol 1999 18 A 1527. 

Murphy B, Li Y, Celia D, et al. Phase III study comparing cisplatin (C) and 5-Fluorouracil (F) versus cisplatin and paclitaxel (T) in metastatic/recurrent head and neck cancer (MHNC). ProcAnnu Meet Am Soc Clin Oncol 2001 20 A894. 

Ball HG, Blessing JA, Lentz SS, Mutch DG. A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium a Gynecologic Oncology Group study. Gynecol Oncol 1996 62 278-81. 

G. Popped, R. Goldbrunner, F.J. Gildehaus, F.W. Kreth, P. Tanner, M. Holtmannspotter, J.C. Tonn, K. Tatsch, 0-(2-[ F]fluoroethyl)-L-tyrosine PET for monitoring the effects of convection-enhanced delivery of paclitaxel in patients with recurrent glioblastoma, Eur. J. Nucl. Med. Mol. Imaging 32(9) (2005) 1018-1025. 

Combination chemotherapy is the standard approach to stage III and stage IV disease. Randomized clinical studies have shown that the combination of paclitaxel and cisplatin provides survival benefit compared with the previous standard combination of cisplatin plus cyclophosphamide. More recently, several studies have shown that carboplatin and paclitaxel yields clinical results similar to what is achieved with the cisplatin plus paclitaxel combination however, because of reduced toxicity and greater ease of administration, carboplatin plus paclitaxel has now become the treatment of choice. In patients who present with recurrent disease, the topoisomerase I inhibitor topotecan, the alkylating agent altretamine, and liposomal doxorubicin are used as single agent monotherapy. 

A number of cytotoxic agents have demonstrated significant singleagent activity in chemotherapy-naive patients with limited- and extensive-disease SCLC, but the activity in recurrent or refractory SCLC is modest. Among the more commonly used chemotherapy agents in the United States are cisplatin, carboplatin, etoposide (intravenous and oral regimens), topotecan, paclitaxel, docetaxel, and gemcitabine. 

The NCCN guidelines recommend retreatment with either paclitaxel or platinum, or the combination of paclitaxel and a platinum compound if disease recurs more than 6 months after the initial treatment with paclitaxel in combination with a platinum analog. Treatment options for patients with refractory disease or disease recurrence within 6 months after treatment include topotecan, altretamine, oral etopo-side, liposomal doxorubicin, gemcitabine, tamoxifen, referral for a clinical trial, or supportive care therapy. 

Pegylated liposomal doxorubicin is an emerging option for patients with recurrent ovarian cancer. In an early phase II study, 35 patients with progressive disease after at least one platinum and paclitaxel-based regimen received pegylated liposomal doxorubicin 50 mg/m every 3 weeks (with a dose reduction to 40 mg/m in the event of grade 3 or 4 toxicities or a lengthening of the interval to... 

Sabbatini P, Brown J, Aghajanian C, Hensley ML, Pezzulli S, Flaherty C, Lovegren M, Funt S, Warner M, Mitchell P, Bolton MG, et al A phase 1/11 study of PG-paclitaxel (CT-2103) in patients (pts) with recurrent ovarian, fallopian tube, or peritoneal cancer, Proc Am Soc Clin Oncol 2002, 21, 1 Pt 2, Abs 871. 

Pending completion of the canine toxicity studies and demonstration of safety, phase I-II clinical trials for pachtaxel-loaded polymer treatment of intracranial tumors are plamned. Paclitaxel in loaded polymer has already been utilized clinically for recurrent ovarian cancer. 

Secord AA, Teoh DK, Barry WT, Yu M, Broadwater G, Havrilesky LJ, Lee PS, Berchuck A, Lancaster J, Wenham RM (2012) A phase 1 trial of dasatinib, an SRC-family kinase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer. Clin Cancer Res 18 5489-5498... 

Cohen MH, Gootenberg J et al. (2007). FDA drug approval summary bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer. Oncologist 12(6) 713-718... 

Avastin was studied in NSCLC and approved in 2006 for NSCLC treatment in combination with carbo-platin and paclitaxel for the initial systemic treatment of patients with unresectable, locally advanced, recurrent or metastatic, non-squamous, non-small cell lung cancer. An improvement in survival time was reported when Avastin was added to a standard chemotherapy regimen. A multi-center clinical trial supporting this approval enrolled 878 patients who had not received prior chemotherapy (Sandler et al. 2006). The trial compared the effectiveness of Avastin plus carboplatin and pacUtaxel with chemotherapy by carboplatin and paclitaxel alone. The median overall survival time for patients in the Avastin plus carboplatin and pacUtaxel arm was 12.3 vs 10.3 months for patients receiving only carboplatin and paclitaxel. 

Kato K, Chin K, Yoshikawa T, Yamaguchi K, Tsuji Y, Esaki T, Sakai K, Kimura M, Hamaguchi T, Shimada Y, Matsumura Y, Ikeda R (2012) Phase II study of NK105, a paclitaxel-incorporating micellar nanoparticle, for previously treated advanced or recurrent gastric cancer. Invest New Drags 30 1621-1627... 

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