Around the early 1980s, there were suggestions that using drug combinations instead of single drugs was to become the "gold standard" of treatment, but results from recent trials question the value of routine combination chemotherapy .
    One problem with combination chemotherapy is the poor complete response rate for all drug programs, with average survival varying between four and nine months. A second problem is that there has been little overall difference in survival for those receiving 5-FU alone or in combinations. The response rate may be higher for a combination, but the toxicity of the programs has to be assessed in light of the overall failure of chemotherapy to improve survival.
    The most common combination recently had been FAM (5-FU + doxorubicin + mitomycin-C), with a response rate of about 20 to 30 percent with little survival advantage and rare complete remission . Other combinations using 5-FU and a variety of drugs—including etoposide , doxorubicin and cisplatin (EAP)—have higher reported response rates. Reports from Europe showed that other combinations were superior to FAM in both response and survival. Some of these are the FAMtx combination (5-FU + doxorubicin + high-dose methotrexate with leucovorin rescue), EAP (etoposide + doxorubicin + cisplatin), which has a high toxicity, ELF (etoposide + leucovorin + 5-FU) and FAP (5-FU + doxorubicin + cisplatin).

Investigational Combinations  A variety of other chemotherapy combinations are currently receiving trials, so far with limited success and little improvement in the survival rate.