The anticancer effect of free HCQ at 200–800 mg/day p.o. has been evaluated in two similar clinical trials on glioblastoma patients in concomitant temozolomide drugs and radiotherapy. Although a dose-dependent significant increase of autophagy markers, no significant effects on tumor suppression were recorded in both studies, as the dose-limiting toxicity was not allowed to achieve higher doses of HCQ [162,165]. The maximum tolerated dose is the dose over which at least one patient from six experienced dose-limiting toxicity, including myelosuppression, anorexia, fatigue, or nausea. Moreover, it has been proved that HCQ severely altered the organization of the Golgi apparatus and the endolysosomal system in C57BL/6JolaHsd mice under 60 mg/kg/day of HCQ i.p. [166]. However, different from Rosenfeld’s studies, no maximum tolerated dose was reached for HCQ in combination with chemotherapic temsirolimus, allowing us to perform a dose-escalation study on 27 patients with solid tumors and 12 with a melanoma diagnosis. In both cases, the standard intravenous dose of temsirolimus with 1200 mg of oral HCQ was considered safe and tolerated and inhibited tumor growth [167]. The same authors further assessed the HCQ anticancer properties and dose-limiting toxicity on 40 patients with metastatic melanoma, by administering a dose intense regimen of temozolomide and escalating doses of HCQ (200–1200 mg/day p.o.). Patients well tolerated the treatment, showing a positive response in the 14% of cases and stability of disease in 27%, due to the modulation of autophagy. No maximum tolerated dose was reached, although common toxicities were manifested [168]. According to the results of Rangwala, a phase I trial on 25 patients with myeloma demonstrated that the recommended dose of HCQ for a phase II trial is 600 mg twice a day. Among eligible patients, 14% experienced a very good response, 14% minor responses, and 45% a period of stability in the disease when the association of HCQ and bortezomib were provided. The synergic effect on myeloma was probably due to the combination of inhibition of HCQ on autophagy and bortezomib on proteasomal degradation, leading to the accumulation of misfolded proteins and autophagic vacuoles in cancer cells [169]. Likewise, doses of 600 mg of HCQ twice a day are not associated with toxicity and its usage as adjuvant therapy with everolimus was well tolerated and produced disease control in 67% of the metastatic clear-cell renal cell carcinoma patients and achieved the rate of six month progression-free survival in 45% of patients [170].