A search for the “Goldilocks zone” with regard to the optimal duration of adjuvant temozolomide in patients with glioblastoma

In astronomy, the “Goldilocks zone” refers to an area of space in which a planet is just the right distance from its home star so that its surface is neither too hot nor too cold to support life. Similarly, there has long been a quest to determine the optimal duration of adjuvant chemotherapy in patients with cancer. Too little adjuvant therapy may result in early relapses and death, while too much could lead to excessive toxicities and costs as well as a reduction in quality of life and perhaps even early death. Randomized clinical trials designed specifically to address this question have been conducted in a wide variety of systemic cancers. These trials have included cancers with very favorable outcomes (germinomas and hematologic malignancies), cancers in which adjuvant therapy improves cure rates (breast, colon, and lung cancer), and cancers (breast, lung, ovarian, and colon) that are metastatic at presentation and where one could make a case for indefinite therapy.^1–6 Data from these trials have consistently demonstrated that extending cytotoxic therapy beyond 4–6 months does not improve survival and have driven treatment guidelines to recommend the more abbreviated regimens, as is evident in the National Comprehensive Cancer Network Guidelines.⁷ The most likely reason for this is that after months of therapy, the surviving cancer cells are likely resistant to the administered chemotherapy.

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