By Dr. Asghar H. Asghar
Abstract:
Head and neck cancer is among the most prevalent cancers in
Pakistan, with many patients presenting with advanced disease
that is not amenable to surgical intervention. In such cases,
alternative treatment modalities, including chemotherapy,
radiotherapy, or best supportive care, are often considered.
However, a significant proportion of these patients are
clinically unfit to tolerate the rigors of chemotherapy or
radiotherapy.
Triple metronomic chemotherapy (TMC) has emerged as a
promising palliative option. Data presented at ASCO from
India, later published in the Journal of Clinical Oncology
(January 2023), highlighted the efficacy of TMC in this
context. The regimen consisted of oral methotrexate (9 mg/m²
once weekly), celecoxib (200 mg twice daily), and erlotinib
(150 mg daily). A variant of this regimen, incorporating
low-dose intravenous nivolumab (TMC-I, 20 mg every three
weeks), demonstrated significantly improved outcomes. The
study reported a one-year overall survival of 16% with TMC
alone versus 43% with TMC-I, and a median overall survival of
6.7 months versus 10.1 months, respectively.
Given the similarities between Pakistan and India in terms of
socioeconomic constraints and healthcare challenges, this
protocol was adapted for patients in Pakistan. Due to the
unavailability of erlotinib, gefitinib was used as a substitute. A
total of 200 patients with locally advanced, unresectable head
and neck cancer were treated in a 1:1 ratio: 100 patients
received TMC, while the remaining 100 received TMC-I.
The results were encouraging, with a partial response rate of
approximately 70% in the TMC group and 80% in the TMC-I
group. Notably, responses were observed within 1-2 months of
initiating treatment. Patient satisfaction rates were high,
reaching nearly 90%. Side effects were minimal, with
occasional instances of oral mucositis or diarrhea. Importantly,
no cases of cytopenia were reported.
Conclusion:
Triple metronomic chemotherapy, alone or in combination with
low-dose nivolumab, is an effective and well-tolerated option
for managing locally advanced head and neck cancer in
patients who are not candidates for surgery, chemotherapy, or
radiotherapy. This regimen offers a viable solution in
resource-constrained settings, providing significant clinical
benefits with minimal adverse effects.