Chloroquine as an Anti-autophagy Drug in Stage IV Small Cell Lung Cancer (SCLC) Patients: A Phase 1 Trial
Tumor hypoxia is a well-known factor negatively influencing outcome in many solid tumors,
including small cell lung cancer. Hypoxic cells are more radio-resistant, more
chemo-resistant and more prone to develop distant metastases than normoxic cells.
One of the mechanisms responsible for survival of these therapy-resistant hypoxic cells is
(macro-)autophagy: a phenomenon in which cells provide themselves with energy (ATP) by
digesting their own cell-organelles. Chloroquine is a potent blocker of autophagy and has
been demonstrated in a lab setting to dramatically enhance tumor response to radiotherapy,
chemotherapy and even anti-hormonal therapy.
Thus, chloroquine might very well be able to increase overall survival in small cell lung
cancer by sensitizing cells resistant to chemotherapy and radiotherapy.
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the toxicity of adding chloroquine in escalating doses in SCLC patients: to standard dose cisplatin-etoposide in extensive disease SCLC; to standard dose concurrent radiotherapy and cisplatin-etoposide in limited disease SCLC
Philippe Lambin, DM, PhD
Maastricht Radiation Oncology
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)