Today we’ll consider the second of the authors’ suggestions: to limit second and third-line treatments to sequential monotherapies for most solid tumors. This particular suggestion, one of the few proposed with which I disagree, falls under the rubric of how oncologists’ behavior might be modified. The authors write:
A Cochrane meta-analysis showed that combination therapy had a small advantage over single agents for first-line therapy but caused more toxicity, and the review left unresolved the question of whether sequential single agents were a better choice.
…patients will live just as long but will avoid toxic effects. Second, society will benefit from cost reductions associated with less chemotherapy, fewer supportive drugs, and fewer toxicity-associated hospitalizations.
This approach is tempting, cost-wise, but may be simplistic: The purpose of combination chemotherapy is to give agents that work additively or synergistically, typically each at a lower dose, to achieve more effective treatment. In cancer, the best-studied multidrug regimens are in lymphoma, leukemia and breast cancer. Similar principles apply to antibiotic regimens for some infectious diseases, such as the drug “cocktails” for HIV or tuberculosis.
It could be that the authors are right for certain agents and some tumor types. But, likely, some drugs, including new targeted treatments given to patients who’ve already had several treatments, may be most effective and, paradoxically, less toxic – because the dose of each drug can be lower. The likelihood of resistant clones emerging may be diminished, too.
The problem we’re left with, of course, is that testing the different combination regimens will be costly. But I wouldn’t assume it’s better or necessarily cost-effective to give cancer drugs one at a time.