Cisplatin 5-FU

Taylor SG, Murthy AK, Caldarelli DD, et al. Combined simultaneous cisplatin/5-FU infusion chemotherapy and split course radiation in head and neck cancer. J Clin Oncol 1989 7 846-856. 

Landry JC, Harris W Yang GY, et al. Neoadjuvant treatment with GEM, cisplatin, 5-FU and accelerated hyperfractionated radiation therapy in advanced GI malignancy. Radiology 2000 217 147. 

Taylor SG, Murthy AK, Griem KL, et al. Concomitant cisplatin/5-FU infusion and radiotherapy in advanced head and neck cancer 8-year analysis of results. HeadNeck 1997 19 684—691. 

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. 

It is interesting to note that the results from our studies at Vanderbilt using lower doses of radiation have led to similar survival rates, local control, and less toxicity when compared to centers using higher doses of radiation. This dose of radiation was based on earlier studies that utilized two cycles of cisplatin, 5-FU, etoposide, and leucovorin with 3000 cGy of radiation followed by resection. The median survival of 24 mo and 2-yr survival of 51% was better than historical controls treated with surgery alone (63,64). 

Our laboratories were the first to use CEPH family cell lines to demonstrate that a significant genetic component contributed to susceptibility to the cytotoxic effects of cisplatin, 5-FU and docetaxel (17,18). Dolan et al. estimated the heritability for susceptibility to cisplatin-induced cytotoxicity to be approximately 0.47 therefore sensitivity to the C5dotoxic effects of cisplatin is under appreciable genetic influence. Linkage analysis was performed and the strongest signal (lod 2.16, empirical /7-value 0.0005) was found on chromosome 1 at 44 cM (18). 

Combination chemotherapy administered concurrent with radiation has produced the most promising results in advanced, unresectable disease. The important study of Merlano et al. randomized 157 patients to conventional radiotherapy vs. cisplatin/5-FU given concurrent with radiation in alternating weekly fashion. They reported a 3-year survival rate of 41% with concurrent therapy vs. 23% with radiation alone (p < 0.05) and 5-year survival rate of 24% vs. 10% (p < 0.02) [136]. Taylor et al. reported significantly improved disease-free survival rates in patients treated with concomitant cis-platin/5-FU and radiation over sequential therapy (17 months vs. 13 months, p = 0.003) in their study of 214 patients with unresectable disease [137]. 

Marked increments in response were observed with the incorporation of cisplatin into combination regimens response rates greater that 50% were reported in Phase-Ill studies of cisplatin/ifosfamide, cisplatin/ifosfamide/ bleomycin, and cisplatin/5-FU [188-190]. Randomized trials of these combinations administered prior to radiotherapy in locally advanced disease have not shown a survival advantage however, a recent GOG trial of concurrent cisplatin or cisplatin/5-FU/hydroxyurea and radiation was associated with significantly improved progression-free survival versus concurrent hydroxyurea and radiation in patients with Stage IIB-IVA cervical cancers [191]. Combined cisplatin and paclitaxel produced responses in 9 of 11 patients in a recent GOG study [192] and will be the focus of larger trials in the future. 

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