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Combined Metronomic Chemo-immunotherapy (CMCI) in Head and Neck Cancers–An Experience from a Developing Country

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Indian Journal of Surgical Oncology Aims and scope Submit manuscript

Abstract

Head and neck squamous cell carcinomas (HNSCC) have proven to be inherently resistant to systemic treatments as a result of histological, molecular, and etiological heterogeneity, with limited responses seen after second-line therapy and beyond. With limited treatment options after progression on systemic chemotherapy in HNSCCs, immunotherapy has a role to play with improved results. In this prospective, observational, non-randomized, open-label study, a total of 12 patients with advanced, relapsed, or metastatic HNSCC received Inj. Nivolumab weight-based dose of 3 mg per kg, intravenously every 2 weeks along with low-dose capecitabine 500 mg twice a day, was prospectively assessed. The patient’s clinical, hematological, and staging characteristics were described and the clinical benefit rate (CBR) was calculated. A total of 12 patients received the combined metronomic chemo-immunotherapy (CMCI). The majority of patients were belonging to ECOG-PS 1(66%), with all patients being in stage IV disease. Six, four, and two patients received immunotherapy as the 5th, 3rd, and 4th line of therapy, respectively. Nivolumab and low-dose capecitabine were used in all 12 patients. CBR was seen in 66% (8/12) of patients, one patient died due to hepatitis and hepatic encephalopathy, another patient died due to pneumonia and respiratory complications, two patients had progressive disease, and two patients with stable disease discontinued treatment because of financial constraints and kept on capecitabine alone. The majority tolerated therapy well with no grade 3/4 immune-related adverse events (IRAEs). Two patients required supportive therapy with packed red cell transfusion and albumin infusions. Six-month overall survival (OS) and progression-free survival (PFS) in the study population were 83.3% and 66.6%, respectively. In conclusion, nivolumab along with metronomic chemotherapy with low-dose capecitabine was very well tolerated and exhibited anti-tumor activity with a CBR of 66%, 6-month OS of 83.3%, and 6-month PFS of 66.6%, in extensively pretreated patients with HNSCCs. Additional studies of nivolumab and metronomic chemotherapy and immuno-immuno combination therapy in these diseases are ongoing.

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Data Availability

All required data is available in the article itself, so if any updates are available we will provide as and when required.

Abbreviations

ECOG:

Eastern Cooperative Oncology Group

Ca BM:

Carcinoma Buccal Mucosa

Ca BOT:

Carcinoma of Base of Tongue

SqCC:

Squamous cell carcinoma

PCV:

Packed cell volume

Alb:

Albumin

PD:

Progressive disease

PR:

Partial response

LFU:

Lost to follow-up

SD:

Stable disease

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Author information

Authors and Affiliations

  1. Department of Medical and Pediatric Oncology and Hematology, J N Medical College and KLE Academy of Higher Education and Research, Belagavi, India

    Irappa Madabhavi

  2. Kerudi Cancer Hospital, Bagalkot, India

    Irappa Madabhavi

  3. Nanjappa Hospital, Davanagere, Karnataka, India

    Irappa Madabhavi

  4. Department of Pulmonary Medicine, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India

    Malay Sarkar

  5. Department of Community Medicine, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India

    Vineet Kumar

  6. Department of Radiation Oncology, J N Medical College, Belagavi, Karnataka, India

    Raghavendra Sagar

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  1. Irappa Madabhavi
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  2. Malay Sarkar
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  3. Vineet Kumar
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  4. Raghavendra Sagar
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Contributions

IM conceived and designed the experiment, made critical revisions, and approved the final version. IM, MS, VK, and RS analyzed the data and wrote the first draft of the manuscript. IM, MS, VK, and RS contributed to the writing of the manuscript. IM, MS, VK, and RS agree with the manuscript results and conclusions. IM, MS, VK, and RS jointly developed the structure and arguments for the paper. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Irappa Madabhavi.

Ethics declarations

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Conflict of Interest

None declared. Initial 2-year data has been accepted in an abstract form in the Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7–10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl): Abstract nr P101.

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Madabhavi, I., Sarkar, M., Kumar, V. et al. Combined Metronomic Chemo-immunotherapy (CMCI) in Head and Neck Cancers–An Experience from a Developing Country. Indian J Surg Oncol (2024). https://doi.org/10.1007/s13193-024-01900-6

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