Neoplasms

Symptoms and General Pathology

All Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Neoplasm Metastasis

Carcinoma

Recurrence

Nasopharyngeal Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Anti-Infective Agents

Antirheumatic Agents

All Drugs and Chemicals

Hydroxychloroquine

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

Hydroxychloroquine (HCQ), is used one day before chemotherapy and radiotherapy, 400-600mg, oral tablet, once. During chemotherapy and radiotherapy, HCQ maintenance dose is 200-400mg daily.

Placebos are used one day before chemotherapy and radiotherapy, and during the therapy.

HCQ, 400-600mg, oral tablet, once, one day before chemotherapy and radiotherapy. During therapy, HCQ maintenance dose is 200-400mg daily.

Placebo, oral tablet, once, one day before chemotherapy and radiotherapy. During therapy, placebo maintenance oral tablet once daily.

Placebo

Bo You, Doctor

Dormant cancer cells that survive anti-cancer therapy can lead to cancer recurrence and disseminated metastases that prove fatal in most cases. Recently, specific dormant polyploid giant cancer cells (PGCC) have drawn our attention because of their association with the clinical risk of nasopharyngeal carcinoma (NPC) recurrence, as demonstrated by previous clinical data. In study, we report the biological properties of PGCC, and reveal that autophagy is a critical mechanism of PGCC induction. Moreover, pharmacological inhibition of autophagy greatly impaired PGCC formation, significantly suppressing metastasis and improving survival in a mouse model. Mechanistically, chemotherapeutic drugs partly damaged mitochondria, and activated autophagy to promote PGCC formation. High numbers of PGCCs correlated with shorter recurrence time and worse survival outcomes in NPC patients. Collectively, these findings suggest a therapeutic approach of targeting dormant PGCCs in cancer.

Pretreatment with an autophagy inhibitor (HCQ) before chemotherapy and radiotherapy could prevent formation of therapy-induced dormant polyploid giant cancer cells, thereby reducing recurrence and metastasis of nasopharyngeal carcinoma.

Although the majority of patients with nasopharyngeal carcinoma (NPC) do not present with overt metastases at diagnosis, a significant number succumb to disseminated disease years after the successful treatment of the primary tumor. Thus, late NPC recurrence may be the result of rare and elusive dormant cancer cells hiding in specialized niches being reactivated by specific signals. The concept of cancer dormancy has been described for the most common solid and hematological cancers; however, the dormant cancer cells in NPC remain largely uncharacterized.

Although many factors contribute toward cancer cell dormancy, recent studies have demonstrated that cancer therapy can induce cellular dormancy. Indeed, therapy-induced dormancy has been shown to lead to durable proliferation arrest, resulting in the formation of polyploid giant cancer cells (PGCCs), which are a unique sub-population of cancer cells that contribute toward the heterogeneity of solid tumors. Unlike regular-sized diploid cancer cells, PGCCs display distinct morphological features, including a large cytoplasmic area and a high genomic content contained within a single highly enlarged nucleus or multiple nuclei. Despite being present in low numbers, the frequency of PGCCs increases markedly after exposure to hypoxia and therapeutic interventions such as radiotherapy and chemotherapies.

Our findings, which used a highly relevant clinical orthotopic model of imageable NPC and clinical data, suggest that autophagy inhibition (HCQ) prevents therapy-induced dormant PGCC formation and thereby prevents NPC metastasis.

Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients

Study protocol, statistical analysis plan, informed consent form, clinical study report, and analytic code will be shared to other researchers.

After the patients are diagnosed and treated, CT scans is used semi-annually to determine the progression, recurrence and metastasis of tumor.

Affiliated Hospital of Nantong University

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients	NCT06389201	Nasopharyngeal ...	HCQ Placebo	20 Years - 70 Years	Affiliated Hospital of Nantong University
Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients	NCT06389201	Nasopharyngeal ...	HCQ Placebo	20 Years - 70 Years	Affiliated Hospital of Nantong University
Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients	NCT06389201	Nasopharyngeal ...	HCQ Placebo	20 Years - 70 Years	Affiliated Hospital of Nantong University

Spots Global Cancer Trial Database for tumor dormancy