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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Oncotarget
2015 ; 6
(18
): 16735-45
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Addition of rapamycin and hydroxychloroquine to metronomic chemotherapy as a
second line treatment results in high salvage rates for refractory metastatic
solid tumors: a pilot safety and effectiveness analysis in a small patient
cohort
#MMPMID25944689
Chi KH
; Ko HL
; Yang KL
; Lee CY
; Chi MS
; Kao SJ
Oncotarget
2015[Jun]; 6
(18
): 16735-45
PMID25944689
show ga
BACKGROUND: Autophagy is an important oncotarget that can be modulated during
anti-cancer therapy. Enhancing autophagy using chemotherapy and rapamycin (Rapa)
treatment and then inhibiting it using hydroxychloroquine (HCQ) could
synergistically improve therapy outcome in cancer patients. It is still unclear
whether addition of Rapa and HCQ to chemotherapy could be used for reversing drug
resistance. PATIENTS AND METHODS: Twenty-five stage IV cancer patients were
identified. They had no clinical response to first-line metronomic chemotherapy;
the patients were salvaged by adding an autophagy inducer (Rapa, 2 mg/day) and an
autophagosome inhibitor (HCQ, 400 mg/day) to their current metronomic
chemotherapy for at least 3 months. Patients included 4 prostate, 4 bladder, 4
lung, 4 breast, 2 colon, and 3 head and neck cancer patients as well as 4 sarcoma
patients. RESULTS: Chemotherapy was administered for a total of 137 months. The
median duration of chemotherapy cycles per patient was 4 months (95% confidence
interval, 3-7 months). The overall response rate to this treatment was of 40%,
with an 84% disease control rate. The most frequent and clinically significant
toxicities were myelotoxicities. Grade ?3 leucopenia occurred in 6 patients
(24%), grade ?3 thrombocytopenia in 8 (32%), and anemia in 3 (12%). None of them
developed febrile neutropenia. Non-hematologic toxicities were fatigue (total
32%, with 1 patient developing grade 3 fatigue), diarrhea (total 20%, 1 patient
developed grade 3 fatigue), reversible grade 3 cardiotoxicity (1 patient), and
grade V liver toxicity from hepatitis B reactivation (1 patient). CONCLUSION: Our
results of Rapa, HCQ and chemotherapy triplet combination suggest autophagy is a
promising oncotarget and warrants further investigation in phase II studies.
|Administration, Metronomic
[MESH]
|Aged
[MESH]
|Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
[MESH]
|Autophagy/*drug effects
[MESH]
|Dose-Response Relationship, Drug
[MESH]
|Female
[MESH]
|Humans
[MESH]
|Hydroxychloroquine/adverse effects/*therapeutic use
[MESH]