TABLE 1.
Phase II clinical trials of autophagy inhibition for cancer therapy
| Conditions | Interventions | Number enrolled | Comment | NCT number | Reference |
|---|---|---|---|---|---|
| Hepatocellular cancer | Sorafenib HCQ | 68 | Response rate increased from 2% to 25%. | NCT03037437 | 62 |
| Non‐small cell lung cancer advanced non‐small cell lung cancer recurrent non‐small cell lung cancer | Paclitaxel Carboplatin HCQ Bevacizumab | 32 | The objective response rate (ORR) and total clinical benefit rate were 47% and 68%, respectively. | NCT01649947 | 61 |
| Colorectal cancer | Vorinostat Regorafenib HCQ | 44 | Showed good tolerability and improved anti‐tumor immunity | NCT02316340 | 58 |
| Rectal cancer colon cancer metastasis adenocarcinoma | HCQ Oxaliplatin Leucovorin 5‐fluorouracil Bevacizumab | 50 | The ORR was 68% with an 11% complete response (CR) rate. | NCT01206530 | 63 |
| Pancreatic cancer | Gemcitabine Abraxane HCQ | 104 | Evans grade histopathologic response was statistically improved (p = 0.00016). | NCT01978184 | 59 |
| Metastatic clear cell renal cell carcinoma | HCQ RAD001 | 40 | Disease control [stable disease + partial response (PR)] occurred in 22 of 33 (67%) evaluable patients. | NCT01510119 | 60 |
| Prostate cancer | HCQ | 64 | Minimal toxicity and some activity in prostate‐specific antigen (PSA) progression after local treatment | NCT00726596 | 64 |
| Carcinoma, intraductal, noninfiltrating DCIS ductal carcinoma in situ | CQ Standard Dose (500 mg/week) CQ Low dose (250 mg/week) Procedure: Breast Biopsy | 12 | PCNA proliferation index of DCIS lesions was reduced compared to untreated controls (p = 0.001). | NCT01023477 | 65 |
| Advanced BRAF mutant melanoma | HCQ Trametinib 2 mg daily dabrafenib 150 mg orally twice a day | 50 | Showed high tolerability and response rate (RR), but failed to meet success criteria for 1‐year PFS rate. | NCT02257424 | 66 |
| Advanced adenocarcinoma metastatic adenocarcinoma | HCQ Abraxane Gemcitabine | 119 | Overall survival at 12 months, the primary endpoint, was not improved. | NCT01506973 | 67 |
| Brain and central nervous system tumors | HCQ TMZ RT | 92 | RT and TMZ combined with HCQ (600 mg/d, dose‐limiting toxicity) did not consistently achieve autophagy inhibition, nor was significant improvement in overall survival observed. | NCT00486603 | 68 |
Abbreviations: CQ, chloroquine; HCQ, hydroxychloroquine; RAD001, Everolimus; RT, Radiation; TMZ, temozolomide.