Table 2.
Human clinical autophagy inhibition trials.
| Published clinical trials | ||||||
|---|---|---|---|---|---|---|
| Tumor type | Inhibitor | Phase | Additional therapy | Clinical response | Autophagy evaluation | Ref. |
| Solid tumors | HCQ | I | Rapamycin, Metronomic cyproterone, docetaxel |
PR 40% SD 44% |
Not evaluated | [134] |
| Solid tumors | HCQ | I | Vorinostat | 1 patient (renal cell carcinoma) durable PR | EM of PBMC for AVs | [64] |
| 2 patients (colorectal cancer) prolonged SD | IHC for LC3II | |||||
| Solid tumors and melanoma | HCQ | I | Temsirolimus |
Solid tumor: SD 67% Melanoma: SD 74% |
EM of PBMC for AVs | [65] |
| Solid tumors and melanoma | HCQ | I | TMZ |
Solid tumor: PR 10% SD 27% Metastatic melanoma: PR 14% SD 27% |
EM of PBMC for AVs | [66] |
| Sarcoma | HCQ | Case series | Rapamycin |
6 PR 3 SD 1 PD |
Evaluation of 18FDG-PET as measure of tumor response after two weeks | [135] |
| Glioblastoma | CQ | III | TMZ and radiation | Median survival 24 mo (controls 11 mo) | Not evaluated | [61] |
| Relapsed glioblastoma | CQ | Case series (n = 5) | Radiation |
2 mo response: 2 PR 1 SD |
Not evaluated | [136] |
| Glioblastoma | HCQ | I/II | TMZ and radiation | Median survival 15.6 months |
Plasma concentrations of HCQ EM of PBMC for mean AVs PBMC LC3-II:Actin ratio |
[67] |
| Glioblastoma | CQ | III | TMZ and radiation | Median survival: 33 months (controls 11 months) | Not evaluated | [14] |
| Brain metastases: NSCLC, SCLC, breast, ovarian | CQ | Pilot | Radiation |
Median OS: 5.7 months PFS of brain metastasis at 1 year 55% |
Not evaluated | [62] |
| Brain metastases: NSCLS, breast cancer | CQ | II | Radiation |
ORR 54% (control 55%) PFS (brain metastasis) at 1 year: 83.9% (control 55.1%) |
Not evaluated | [63] |
| Refractory myeloma | HCQ | I | Bortezomib |
14% very good PR 45% period of SD |
Plasma concentrations of HCQ EM of PBMC and bone marrow plasma cells for mean AVs PBMC LC3-II:Actin ratio |
[68] |
| Metastatic PDAC | HCQ | II | None |
Median PFS 1.5 mo OS: 2.3 mo |
PBMC LC3-II:β-Actin ratio | [69] |
| PDAC | HCQ | I/II | Gemcitabine | 61% decreased CA19-9 | LC3-II in PBMC If >51% increase, OS 34.83 months v 10.83 months | [74] |
| NSCLC | HCQ | I | Erlotinib | ORR 5% | Plasma concentrations of HCQ | [137] |
| Ongoing clinical trials | ||||||
|---|---|---|---|---|---|---|
| Tumor type | Inhibitor | Phase | Additional therapy | Clinical response | Autophagy marker | Ref. |
| Colorectal | HCQ | I/II | FOLFOX + Bevacizumab | Ongoing | JNK1 | [138] |
| Glioblastoma | CQ | I/II | Temozolomide + radiation | Ongoing | EGFRvIII | [133] |
| Glioblastoma, HGG, DIPG | CQ | III |
Temozolomide Valproic acid |
Ongoing | None | [139] |
| Pancreatic | HCQ, nab-Paclitaxel | I/II | Gemcitabine, nab-Paclitaxel | Ongoing | Mutant RAS | [128] |
| Pancreatic | HCQ, nab-Paclitaxel | II | Gemcitabine, nab-Paclitaxel | Ongoing | Mutant RAS | [140] |
| Pancreatic | HCQ | I/II | Gemcitabine | Ongoing | Mutant RAS | [141] |
| Pancreatic | HCQ | I | Trametinib | Ongoing | Mutant RAS | [128] |
| BRAF Mutant Melanoma | HCQ | I | Vemurafenib | Ongoing | Mutant BRAF | [142] |
| BRAF Mutant Melanoma | HCQ | I/II | Dabrafenib, Trametinib | Ongoing | Mutant BRAF | [143] |
| NRAS Mutant Melanoma | HCQ | I | Trametinib | Ongoing | Mutant NRAS | [125] |
| Hepatocelluar | HCQ | II | Sorafenib | Ongoing | None | [144] |
| Osteosarcoma | HCQ | I/11 | Gemcitabine, Docetaxel | Ongoing | None | [145] |
| Breast cancer | HCQ | I/II | Palbociclib Letrozole | Ongoing |
ER positive HER2 negative |
[146] |
| Non-small cell lung cancer | HCQ | II | Erlotinib | Ongoing | EGFR | [132] |