Rituximab in combination with gemcitabine plus cisplatin in patients with recurrent and metastatic head and neck squamous cell carcinoma: a phase I trial.

BACKGROUND: The treatment of recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC) remains challenging. Preclinical studies revealed that B cell depletion could modulate the microenvironment and overcome chemoresistance. We conducted a phase I study to evaluate the feasibility and safety of B cell depletion using the anti-CD20 antibody rituximab to treat HNSCC. METHODS: Ten patients were enrolled in two protocols. The first four patients treated using protocol 1 received rituximab 1000 mg on days -14 and -7, followed by gemcitabine/cisplatin every 3 weeks, and rituximab was administered every 6 months thereafter. Because of disease hyperprogression, protocol 1 was amended to protocol 2, which consisted of the concomitant administration of rituximab 375 mg/m2 and gemcitabine/cisplatin every 3 weeks. Another six patients were enrolled and treated using protocol 2. RESULTS: Three patients treated using protocol 1 exhibited rapid disease progression, and the remaining patient could not undergo evaluation after rituximab treatment. Conversely, no unpredicted harm was observed in the six patients treated using protocol 2. Among these patients, one achieved complete response, and two had partial responses. The disease-free durations in these patients were 7.0, 6.2, and 7.1 months, respectively. Immune cell analysis revealed a higher ratio of cytotoxic T cells to regulatory T cells in responders than in non-responders. CONCLUSIONS: B cell depletion using rituximab alone in patients with HNSCC can cause hyperprogressive disease. Contrarily, the co-administration of rituximab and cisplatin/gemcitabine was feasible and safe. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04361409 , 24 April 2020, retrospectively registered.

[18F]-Fluorodeoxyglucose Positron Emission Tomography Standardized Uptake Value as a Predictor of Adjuvant Chemotherapy Benefits in Patients With Nasopharyngeal Carcinoma.

BACKGROUND: The role of adjuvant chemotherapy for the treatment of nasopharyngeal carcinoma (NPC) is controversial, and the identification of adequate predictive factors is warranted. Therefore, we aimed to investigate whether the mean standardized uptake value (SUV) measured on [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) could predict the survival benefits for NPC patients that receive adjuvant chemotherapy. MATERIALS AND METHODS: The data for 174 NPC patients who underwent PET/computed tomography before chemoradiation between January 2004 and January 2012 were reviewed. The SUV75% was recorded for primary tumors. All patients received intensity-modulated radiotherapy and cisplatin-based chemotherapy. Adjuvant chemotherapy consisted of 3 cycles of 75 mg/m(2) cisplatin and 1,000 mg/m(2) fluorouracil for 4 days. RESULTS: The optimal cutoff value was 8.35 for SUV75%, with 112 (64.4%) patients having lower SUV75% and 62 (35.6%) having higher SUV75%. Patients with lower SUV75% had significantly better 5-year overall survival (OS) and distant metastasis-free survival. Multivariate analysis revealed that tumor stage, SUV75%, and adjuvant chemotherapy were significant prognostic factors for OS. Patients with higher SUV75% had significantly higher 5-year OS rates with adjuvant chemotherapy than without adjuvant chemotherapy (84.3% vs. 32.4%, respectively; p < .001). However, in the lower SUV75% group, no differences in 5-year OS were observed between patients who received and those who did not receive adjuvant chemotherapy (92.4% vs. 93.3%, respectively; p = .682). CONCLUSION: The SUV75% on FDG PET for primary tumors could successfully identify NPC patients who may benefit from adjuvant chemotherapy.

ADAM9 enhances CDCP1 protein expression by suppressing miR-218 for lung tumor metastasis.

Metastasis is the leading cause of death in cancer patients due to the difficulty of controlling this complex process. MicroRNAs (miRNA), endogenous noncoding short RNAs with important biological and pathological functions, may play a regulatory role during cancer metastasis, but this role has yet to be fully defined. We previously demonstrated that ADAM9 enhanced the expression of the pro-migratory protein CDCP1 to promote lung metastasis; however, the regulatory process remains unknown. Here we demonstrate that endogenous miR-218, which is abundant in normal lung tissue but suppressed in lung tumors, is regulated during the process of ADAM9-mediated CDCP1 expression. Suppression of miR-218 was associated with high migration ability in lung cancer cells. Direct interaction between miR-218 and the 3'-UTR of CDCP1 mRNAs was detected in luciferase-based transcription reporter assays. CDCP1 protein levels decreased as expression levels of miR-218 increased, and increased in cells treated with miR-218 antagomirs. Induction of miR-218 inhibited tumor cell mobility, anchorage-free survival, and tumor-initiating cell formation in vitro and delayed tumor metastases in mice. Our findings revealed an integrative tumor suppressor function of miR-218 in lung carcinogenesis and metastasis.