Prospective randomised trial of early cytotoxic therapy for recurrent colorectal carcinoma detected by serum CEA.

Abstract

SUMMARY Of 663 patients treated with radical surgery for colorectal cancer, 52 showed a progressive rise in serum carcinoembryonic antigen (CEA) with no other evidence of recurrent disease and were randomised in a prospective study of chemotherapy. Twenty six patients in the treatment group received 5FU and methyl CCNU from the time of randomisation and the remaining 26 controls were given further therapy only if there were clinical indications. All patients were followed for five years or until their death and all but one (control) developed clinical evidence of recurrence. Overall there was no significant difference between the two groups with respect to disease free interval and survival. Whereas the rise in CEA in controls was generally progressive, marked inflections on the CEA curves were seen in the majority of patients receiving early treatment. Eight of 26 treated patients showed a fall in CEA of greater than 20% two months after starting therapy. These patients had a median disease free interval of 90 weeks and a median survival of 107 weeks, these figures being longer than those of treated patients who did not show a fall in CEA and control patients. The serum CEA therefore appeared to give important prognostic information in patients receiving cytotoxic treatment. Early therapy was generally well tolerated.

Inhibition of tumour growth by marimastat in a human xenograft model of gastric cancer: relationship with levels of circulating CEA

“…Tumour antigen levels have been used for many years in the clinical management of cancer (Goldenberg et al, 1981). They have proved of value in detecting recurrent disease (NIH Consensus Statement, 1981;Hida et al, 1996), monitoring the effects of chemotherapy and predicting prolonged survival (Hine and Dykes, 1984;AllenMersh et al, 1987;Ward et al, 1993). A combined analysis of marimastat clinical trials, in patients with carcinoma of the pancreas, ovary, colon and prostate, has demonstrated a dose-dependent reduction in the rate of rise of cancer antigens (Nemunaitis et al, 1998).…”

Serum CEA testing in the post-operative surveillance of colorectal carcinoma

“…In advanced disease a clinical response rate to chemotherapy of over 40% has been reported (Moertel et al, 1975) although this has not been matched by an improvement in survival of treated patients (Buroker et al, 1978). In a study from our unit when cytotoxic therapy was given at the earliest evidence of recurrence, as indicated by a rise in CEA, a similar picture emerged with no overall benefit to treated patients in terms of survival (Hine & Dykes, 1984). However, a subgroup of patients who showed a significant fall in CEA seemed to derive clinical benefit from early therapy (Hine & Dykes, 1984).…”

“…Patients in whom routine screening showed a CEA concentration of > 20 ng ml-1 were recalled to clinic within 2 (Hine & Dykes, 1984).…”

Survival benefit of chemotherapy in metastatic colorectal cancer: a meta-analysis of randomized controlled trials

“…They had a total of 614 patients comparing chemotherapy to an initial observation arm in patients with metastatic colorectal cancer (Hine and Dykes, 1984;Nordic Gastrointestinal Tumour Adjuvant Therapy Group (NGTATG), 1992;Rougier et al, 1992;Scheithauer et al, 1993;Allen-Mersh et al, 1994;Hafstrom et al, 1994;Glimelius et al, 1995). These are listed in Table 1, along with a brief description of treatment schedules.…”

“…A leading oncology text only references one study on this topic (Hine and Dykes, 1984;Cohen et al, 1997). This results in uncertainty for both patient and physician contemplating systemic therapy.…”