A phase I/II trial of concurrent immunotherapy with chemoradiation in locally advanced larynx cancer

Frankart, A.J.; Sadraei, Nooshin Hashemi; Huth, Bradley J.; Redmond, Kevin P.; Barrett, William L.; Kurtzweil, Nicky; Riaz, Muhammad Kashif; Wise‐Draper, Trisha M.; Rodriguez, Cristina P.; Adelstein, David J.; Takiar, Vinita

doi:10.1002/lio2.780

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…9 out of 9 patients achieved surgery free survival when assessed for up to 18 months. 34 Based on the above findings it can be stated that immunotherapy might be more effective in advanced stages compared to initial stages. Also, the effectiveness in initial stages is not as strongly established as in advanced stages.…”

Section: Introductionmentioning

confidence: 90%

Immunomodulatory Therapy in Head and Neck Squamous Cell Carcinoma: Recent Advances and Clinical Prospects

Khadela

Shah

Mistry

et al. 2023

Technol Cancer Res Treat

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The immune system plays a significant role in the development, invasion, progression, and metastasis of head and neck cancer. Over the last decade, the emergence of immunotherapy has irreversibly altered the paradigm of cancer treatment. The current treatment modalities for head and neck squamous cell carcinoma (HNSCC) include surgery, radiotherapy, and adjuvant or neoadjuvant chemotherapy which has failed to provide satisfactory clinical outcomes. To encounter this, there is a need for a novel or targeted therapy such as immunological targets along with conventional treatment strategy for optimal therapeutic outcomes. The immune system can contribute to promoting metastasis, angiogenesis, and growth by exploiting the tumor's influence on the microenvironment. Immunological targets have been found effective in recent clinical studies and have shown promising results. This review outlines the important immunological targets and the medications acting on them that have already been explored, are currently under clinical trials and are further being targeted.

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Section: Introductionmentioning

confidence: 90%

Immunomodulatory Therapy in Head and Neck Squamous Cell Carcinoma: Recent Advances and Clinical Prospects

Khadela

Shah

Mistry

et al. 2023

Technol Cancer Res Treat

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“…Table 1 summarises recent clinical studies involving cisplatin derivatives. Pembrolizumab plus a high dose of cisplatin and radiation Larynx cancer The therapy was safe and showed effectiveness, but more data and longer-term monitoring are needed 2022 [22] Stereotactic body radiotherapy and a full dose of cisplatin or carboplatin…”

Section: Cisplatin Derivativesmentioning

confidence: 99%

Can Cisplatin Therapy Be Improved? Pathways That Can Be Targeted

Ali

Aouida

Sulaiman

et al. 2022

IJMS

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Cisplatin (cis-diamminedichloroplatinum (II)) is the oldest known chemotherapeutic agent. Since the identification of its anti-tumour activity, it earned a remarkable place as a treatment of choice for several cancer types. It remains effective against testicular, bladder, lung, head and neck, ovarian, and other cancers. Cisplatin treatment triggers different cellular responses. However, it exerts its cytotoxic effects by generating inter-strand and intra-strand crosslinks in DNA. Tumour cells often develop tolerance mechanisms by effectively repairing cisplatin-induced DNA lesions or tolerate the damage by adopting translesion DNA synthesis. Cisplatin-associated nephrotoxicity is also a huge challenge for effective therapy. Several preclinical and clinical studies attempted to understand the major limitations associated with cisplatin therapy, and so far, there is no definitive solution. As such, a more comprehensive molecular and genetic profiling of patients is needed to identify those individuals that can benefit from platinum therapy. Additionally, the treatment regimen can be improved by combining cisplatin with certain molecular targeted therapies to achieve a balance between tumour toxicity and tolerance mechanisms. In this review, we discuss the importance of various biological processes that contribute to the resistance of cisplatin and its derivatives. We aim to highlight the processes that can be modulated to suppress cisplatin resistance and provide an insight into the role of uptake transporters in enhancing drug efficacy.

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A phase I/II trial of concurrent immunotherapy with chemoradiation in locally advanced larynx cancer

Frankart

Sadraei

Huth

et al. 2022

Laryngoscope Investig Oto

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Objectives Cisplatin‐based chemoradiation is an established organ‐preserving strategy for locally advanced laryngeal cancer, but long‐term survival remains suboptimal. Immunotherapy has been studied in the metastatic and unresectable recurrent settings. However, additional data are needed to assess its role in organ preservation for locally advanced laryngeal cancer. Methods This trial was an open‐label, single‐arm, multi‐institutional study with a Phase I run‐in portion followed by a planned Phase II component, which closed early due to low accrual. Study patients had Stage III or IV (T2–3; N0–3; M0) laryngeal squamous cell carcinoma and were candidates for larynx preservation. Pembrolizumab was given 2–3 weeks prior to chemoradiation and then, q21 days concurrently with high‐dose cisplatin and radiation prescribed to a total dose of 70 Gy. The primary endpoint of the trial was organ‐preservation rate (OPR) at 18 months. Results A total of nine patients were enrolled with a median follow‐up of 30.1 months. No patient required laryngectomy, resulting in 100% OPR at 18 months. The 12‐month overall survival (OS) rate was 77.8% and the median duration of OS was not reached. All acute Grade 4 (n = 3) toxicities occurred in a single patient with poorly controlled diabetes at baseline. One patient had late Grade 4 laryngeal edema requiring tracheostomy 8 months after chemoradiation, which self‐resolved. Conclusion UCCI‐HN‐15‐02 demonstrated the safety of the addition of immunotherapy to definitive chemoradiation and the patient outcomes suggest the potential for improving long‐term survival while minimizing negative impact from treatment. While results from this trial were promising, a randomized study with a larger number of patients and longer follow‐up is warranted to verify this treatment approach prior to wider adoption. NCT #: NCT02759575. Level of evidence: 2b

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A phase I/II trial of concurrent immunotherapy with chemoradiation in locally advanced larynx cancer

Cited by 4 publications

References 34 publications

Immunomodulatory Therapy in Head and Neck Squamous Cell Carcinoma: Recent Advances and Clinical Prospects

Immunomodulatory Therapy in Head and Neck Squamous Cell Carcinoma: Recent Advances and Clinical Prospects

Can Cisplatin Therapy Be Improved? Pathways That Can Be Targeted

A phase I/II trial of concurrent immunotherapy with chemoradiation in locally advanced larynx cancer

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