A phase II study of mitomycin C, cisplatin and continuous infusion 5-fluorouracil (MCF) in the treatment of patients with carcinoma of unknown primary site

Abstract

Newcastle-upon-Tyne NE1, UK Carcinoma of unknown primary site remains a common clinical diagnosis, accounting for between 5 and 10% of all cancer patients. Numerous combination chemotherapy regimens have been used in the management of carcinoma of unknown primary site, resulting in response rates of 0 -48%. We present the results of a single centre phase II study of the use of the combination of mitomycin C (7 mg m 72 on day 1 of cycles 1, 3 and 5) cisplatin (60 mg m 72 on day 1) and continuous infusion 5-fluorouracil (300 mg m 72 daily), MCF, delivered as a 21-day cycle, in patients with carcinoma of unknown primary site. Thirty-one patients with a diagnosis of carcinoma of unknown primary site were treated in Aberdeen Royal Infirmary between 1997 and 2001 with MCF. In total, 136 cycles of MCF were delivered (median of 5 cycles per patient). Toxicity was acceptable, with 19% grade 3 or 4 neutropenia, 16% grade 3 or 4 thrombocytopenia and 13% grade 3 or 4 nausea and vomiting. No cases of neutropenic sepsis were seen and there were no treatment-related deaths, however, six patients developed thrombotic complications. The overall response rate was 27% (CR 3%; PR 23%). Median time to progression was 3.4 months (95% CI 1.1 -5.6 months) and median overall survival was 7.7 months (95% CI 5.7 -9.8 months). Survival at 1 year was 28%, and at 2 years, 10%. MCF is a tolerable regimen with comparable toxicity, response rates and survival data to most platinum-based combination chemotherapy regimens in use for this devastating disease.

Evaluation of survival benefits by platinums and taxanes for an unfavourable subset of carcinoma of unknown primary: a systematic review and meta-analysis

“…There was one consecutive case series study (Gill et al , 1991) and the other 23 studies were single arm clinical trials (Raber et al , 1991; Briasoulis et al , 1998, 2000, 2008; Parnis et al , 2000; Greco et al , 2001, 2002; Guardiola et al , 2001; Macdonald et al , 2002; Balana et al , 2003; Mukai et al , 2003, 2010; Park et al , 2004; Piga et al , 2004; Pouessel et al , 2004; El-Rayes et al , 2005; Pittman et al , 2006; Schneider et al , 2007; Pentheroudakis et al , 2008; Hainsworth et al , 2009; Schuette et al , 2009; Yonemori et al , 2009; Moller et al , 2010). Three trials (Briasoulis et al , 1998, 2000; Pentheroudakis et al , 2008) also involved a small proportion of favourable CUP patients in their studies, and we extracted the data only from the unfavourable subset.…”

“…Two independent reviewers evaluated the responses, which were the primary outcome of the study in only two studies (Culine et al , 2003; Moller et al , 2010). In all, 14 studies reported prospective calculation of the study size (Greco et al , 2002; Macdonald et al , 2002; Pouessel et al , 2004; El-Rayes et al , 2005; Palmeri et al , 2006; Pittman et al , 2006; Schneider et al , 2007; Pentheroudakis et al , 2008; Hainsworth et al , 2009, 2010; Huebner et al , 2009; Schuette et al , 2009; Yonemori et al , 2009; Mukai et al , 2010). Among the RCTs, only one study had a clear description of the method of allocation concealment (Assersohn et al , 2003).…”

Redefining cancer of unknown primary: Is precision medicine really shifting the paradigm?

“…Table 1 presents all existing randomized trials specifically studying CUP patients, with the regimens and their respective median overall survival and response rates when available [11,[74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89]. As described, the prognostic classification (based on performance status and LDH levels) separates a favourable prognosis subgroup (median survival of 12 months) from a poor prognosis subgroup (median survival of 4 months); for the latter, best supportive care should also be considered upfront in the management algorithm [3,13].…”

Phase II trials in patients with carcinoma of unknown primary: a pooled data analysis

“…Thirty-four regimens were administered as first-line treatment in 1,380 patients. Under front-line regimen, the overall ORR was 430/1,380 (31%, [27][28][29][30][31][32][33]) and the non-progression rate was 731/1,206 (60% [57-63]). The median overall survival was 8 months and the progression-free survival was 4.2 months.…”