Assessment Of Hematological Toxicity in Head and Neck Cancer (HNCS) Patients Receiving Platinum Compounds Chemotherapy at a Tertiary Care Hospital

Head and neck cancers (HNCs), also referred to as head and neck squamous cell carcinomas (HNSCCs), primarily originate from the squamous epithelial cells lining the oral cavity, pharynx, and larynx. Less commonly, HNCs may also arise in the paranasal sinuses, salivary glands, or associated muscles and nerves. ^[1] Globally, head and neck cancers account for more than 400,000 deaths annually, with India projected to experience a 57.5% increase in new cases by 2040.  

Epidemiological data indicate a higher prevalence in males compared to females, with a ratio of approximately 2:1. ^[3] Hematological toxicity, or cytopenia, is a common adverse effect of chemotherapy characterized by a reduction in all three major blood cell lines—red blood cells (RBCs), white blood cells (WBCs), and platelets. A decrease in RBCs leads to anemia, reduced WBCs—particularly neutrophils—causes leukopenia and neutropenia, while diminished platelet counts result in thrombocytopenia. When all three blood cell components are simultaneously suppressed due to impaired bone marrow activity, the condition is referred to as myelosuppression. ^[4] Platinum-based chemotherapeutic agents are widely used in the management of various malignancies but are well known for inducing hematological toxicities through bone marrow suppression and decreased hematopoietic activity. These agents, including cisplatin (CDDP), carboplatin (CBDCA), and oxaliplatin, can cause varying degrees of leukopenia, neutropenia, thrombocytopenia, and anemia. Among them, carboplatin’s dose-limiting toxicity is predominantly myelosuppression, whereas cisplatin is more frequently associated with gastrointestinal and nephrotoxic effects but exhibits relatively lower hematological toxicity. ^[5,6] The severity of these hematologic adverse effects is closely associated with the dose and duration of therapy, as well as patient-specific factors such as age, race, and renal function. Therefore, patients undergoing platinum-based chemotherapy are routinely monitored for hematologic parameters, including absolute neutrophil count (ANC), platelet count, and total WBC count, to ensure timely detection and management of myelosuppressive complications. ^[5] The Common Terminology Criteria for Adverse Events (CTCAE) is widely utilized in clinical trials for the standardized documentation and grading of treatment-related toxicities. The current version, CTCAE v5.0, grades adverse events on a five-point scale:

• Grade 1: Mild
• Grade 2: Moderate
• Grade 3: Severe
• Grade 4: Life-threatening
• Grade 5: Death ^[7,8]

In patients with head and neck cancers (HNCs) receiving concurrent chemoradiation therapy (CRT), hematologic toxicities are particularly relevant due to the combined suppressive effects of chemotherapy and radiotherapy. Studies have shown that most patients undergoing CRT present with advanced-stage disease (75.0%) and laryngeal tumors (87.5%), with nearly half experiencing treatment-related hematologic toxicities and therapy delays. ^[9]

Comparative analyses have revealed that carboplatin demonstrates a higher incidence of hematologic adverse effects, especially thrombocytopenia and neutropenia, when compared with cisplatin. ^[10] Although these toxicities can be managed through growth factor support and blood transfusions, they may significantly impact treatment continuity, increase the risk of infection, and ultimately influence patient outcomes and quality of life (QOL). ^[11]

METHODS

Study design and setting: This was a prospective, observational study conducted in the Oncology Department of Geetanjali Medical College and Hospital (GMCH), Udaipur, Rajasthan, India. The study ran for six months and was approved by the Institutional Ethics Committee (Approval No: GU/HREC/EC/2024/2617). Written informed consent was obtained from all participants before enrollment.

Participants: The study included patients diagnosed with head and neck cancers (HNCs) who were receiving platinum compound–based chemotherapy. Both male and female patients of all age groups were eligible. Patients with cancers other than HNCs and pregnant or lactating women were excluded.

Sample size: Using Cochran’s formula, the minimum required sample size was determined to be 120 patients.

Study Tools: Data were collected through inpatient medical records at GMCH, a pre-designed Patient Data Collection Form (DCF), informed consent forms in English and the local language, the Common Terminology Criteria for Adverse Events (CTCAE) scale, and the Adverse Drug Reaction (ADR) reporting form developed by the Indian Pharmacopoeia Commission.

Plan of study: Participants were screened during ward visits in the Oncology department. Screening was based on the inclusion and exclusion criteria. The purpose, procedures, and requirements of the study were explained to patients and their caregivers, and informed consent was obtained in the language they best understood. A specially designed data collection sheet was used to record socio-demographic details, medical and medication history, and follow-up information. Data were extracted from patient medical records, and ADRs were assessed using the CTCAE scale. If an ADR was identified, an ADR form was completed and reported to the treating physician.

Statistical analysis: Data were analyzed using Microsoft Excel and SPSS software. Descriptive statistics were applied for demographic characteristics, while the Wilcoxon rank-sum test and chi-square test were used for comparisons. A p-value of <0.05 was considered statistically significant. Hematological toxicity in HNC patients was specifically assessed using the CTCAE scale.

Data management and confidentiality: All data were anonymized and coded before analysis to protect patient identity. Access to raw data was restricted to the principal investigator and authorized study team members. Electronic records were stored on password-protected computers, and physical documents were secured in locked cabinets. Confidentiality was strictly maintained, and no identifying information was disclosed in reports or publications.

RESULTS

1. Age-Wise Distribution of Hematological Toxicity

Hematological toxicity varied across age groups. The 41–50 years group showed the highest number of Grade 1 toxicities (n=58), followed by the 51–60 years group (n=39) and 31–40 years group (n=29). Grade 2 toxicities were most frequent in the 31–40 years group (n=12), whereas Grade 3 toxicities were observed mainly in the 31–40, 41–50, and 51–60 years groups, with 15 cases each. Minimal cases were reported in the 21–30, 61–70, 71–80, and 81–90 years age ranges.

2. Rural vs. Urban Distribution

A total of 238 hematological toxicity cases were recorded across rural and urban populations. Majority of Grade 1 toxicities occurred in the rural population (n=134) compared to urban (n=16). Similarly, Grade 2 toxicities were more common in rural patients (n=29) than urban (n=5). Grade 3 toxicities were also predominantly reported in rural areas (n=47), while only 7 cases were noted in the urban group.

3. Hematological Toxicity Across Treatment Cycles

Toxicities were distributed variably across different treatment cycles. The maximum number of Grade 1 toxicities was reported during Cycle 1 (n=65), followed by Cycle 2 (n=38) and Cycle 3 (n=33). Grade 2 toxicities were equal in Cycle 1 and Cycle 2 (n=12 each). Grade 3 toxicities were more prominent in Cycle 1 (n=26), while decreasing trends were observed in subsequent cycles—Cycle 2 (n=18), Cycle 3 (n=4), and Cycle 4–6 with minimal occurrences.

4. Distribution by Treatment Type

When comparing different treatment types, the NACT group recorded the highest number of Grade 1 toxicities (n=72), followed by TPF (n=34), Palliative (n=31), and Concurrent Chemoradiation (n=13). Grade 2 toxicities were most frequent in NACT (n=13), followed by Palliative (n=9) and TPF (n=10). Grade 3 toxicities were mainly observed in the Palliative group (n=15), followed by NACT (n=21), TPF (n=14), and Concurrent Chemoradiation (n=4).

5. Comparison Between Cisplatin and Carboplatin

Among the two drug regimens, Cisplatin was associated with a higher number of Grade 1 toxicities (n=92) compared to Carboplatin (n=58). However, Grade 2 toxicities were more frequent in the Carboplatin group (n=21) than in Cisplatin (n=13). Grade 3 toxicities were slightly higher in patients receiving Cisplatin (n=32) as compared to Carboplatin (n=22).

6. Gender-Wise Distribution

Out of the total cases analyzed, males exhibited a greater number of hematological toxicities compared to females. Grade 1 toxicities were more common in males (n=107) than females (n=43). Similarly, Grade 2 toxicities were recorded in 23 males and 11 females. Grade 3 toxicities also followed the same pattern, with 41 cases among males and 13 among females.