Ambispective Study of the Toxicological Profile of Cisplatin in Head and Neck Squamous Cell Carcinoma

The majority of Oral cavity malignancies are squamous cell carcinomas, arising from the epithelial lining of the upper aero digestive tract. Due to the anatomical complexity and the critical functions performed by this region, such as breathing, speech, swallowing, and facial expression, oral cavity cancers present unique clinical and therapeutic challenges.

Globally, oral cavity cancer represents a significant public health burden, with a particularly high incidence in South and Southeast Asia. This increased prevalence is strongly associated with the widespread use of tobacco in both smoked and smokeless forms, alcohol consumption, and the habitual chewing of betel quid and areca nut. In recent decades, infection with high-risk strains of human papillomavirus (HPV), especially HPV-16, has emerged as a major etiological factor, particularly in cancers of the oropharynx. Environmental exposures, occupational hazards, poor oral hygiene, nutritional deficiencies, and genetic susceptibility also contribute to disease development.

The clinical presentation of Oral cavity cancer varies depending on the site and stage of the tumor. Common symptoms include non-healing ulcers in the mouth, persistent sore throat, dysphagia, hoarseness of voice, nasal obstruction or bleeding, unexplained weight loss, and the presence of a painless neck mass due to regional lymph node involvement. Early-stage disease may be asymptomatic or present with mild, non-specific symptoms, leading to delays in diagnosis. As a result, a significant proportion of patients are diagnosed at advanced stages, which adversely affects prognosis and increases the complexity of treatment._[1]

ETIOLOGY:

1. Human Papilloma Virus: A highly common DNA virus, which is transmitted by sexual contact, transmission from mother to child and through contamination. HPV contains two active viral genes i.e., E6 AND E7.
2. Tobacco and Smoking: Cigarettes, tobacco, cigars, pipes and smokeless tobacco (like ghutka, khaini, betel quid with tobacco). 90% of cancer risk can be attributed to tobacco. Tobacco contains nearly more than thirty known carcinogens.
3. Alcohol consumption: The solvent effect of alcohol enhances the penetration of tobacco carcinogens which leads to development of Erythroplakia and Leukoplakia (patches and lesions in oral cavity).
4. HIV: Almost 5 percent of patients with head and neck cancer. Over 20percent of head and neck cancer patients suffered by non-HIV patients.
5. Immunosuppression: Multiple factors like HIV, infections, organ transplant recipients reduced immune surveillance
6. Premalignant lesion’s: Presence of precancerous lesions in other organs.
7. Poor hygiene: Brushing teeth once daily, use of painful or ill-fitting dentures - which causes oropharyngeal cancer, occupational exposure to organic chemicals, coal products, cement, paint and wood dust. _[2]

EPIDEMOLOGY: Every year, about 6 lakh cases of Oral cavity cancer are diagnosed worldwide, with 3,00,000 individuals dying. Every year, around 11,000 new cases of HPV (Human Papilloma Virus)-related Oral cavity cancer are diagnosed in the United States _[3]

SIGNS & SYMPTOMS [29,30] White patches, red patches, mouth ulcers/sores, lump or mass in the neck, persistent moth pain, difficulty chewing(dysphagia), loose teeth, difficulty in opening mouth(trismus), Painless lump in cheek(parotid), under jaw(submandibular), under the tongue (sublingual), facial weakness or paralysis, facial numbness, twitching of facial muscles, palatal mass or ulcer, trismus, unintended weight loss, persistent dry mouth. _[4]

INCIDENCE: Male to female incidence ratio is 3:1 and about 70% of new cases occur in low- and middle-income countries. In 2018 there were an estimated 453,000 deaths from oral cavity cancer globally. Oral cavity cancer in India was found to impose a high prevalence, incidence and mortality rate. _[5]

PREVELANCE: According to the International classification of disease related health, based on anatomical location of tumor. The data extracted for both incidence and prevalence. The highest prevalence rate was reported for lip and oral cavity cancer which was 26.31 for 5 years in 1,00,000 individuals. _[5]

RISK FACTORS: Cigarette smoking, tobacco and alcohol consumption, stress, nicotine, poor oral hygiene, radiation exposure, occupational exposure, immunodeficiency, gastroesophageal reflux disease, human papilloma virus, Epstein-bar virus. _[6]

PATHOPHYSIOLOGY:

Tobacco/ Cigarette + HPV + Premalignant lesions + Poor hygiene/occupational exposure + Alcohol + Tar consumption + Genetics + HIV, HSV, EBR viruses + Chewable tobacco (Betel quid)

These factors contain carcinogens like nitrosamines; N-nitrosonorornicotine; Ethanol directly effects NMDA GABA; HPV effects E6, E7 virus

 

 

Accumulation of genetic and molecular alterations

 

 

Inactivation and mutations of tumor suppressor p53 gene

 

 

Amplification of Oncogenes like CCND1 and EGFR disruption of cell cycle

Deregulated proliferation leads to    premalignant, genetically abnormal cells

Genomic instability leads to rapid cell cycling

 

 

Increased production of HGF to enhance tumor cell proliferation, invasion, metastasis.

 

 

Activation of more than 60 target genes

Initiates process of Metabolism, Cell adhesion, Cell cycle arrest, Angiogenesis, cellular proliferation

Activates the downstream MAP kinase signaling cascade

 

 

Increase in cytokines, IL-6, TNF, IF and increase in growth factor TGF-Beta

 

 

Promotes cell proliferation and angiogenesis

 

 

Cell growth arrest and Apoptosis _[7]

 

 

BRAND NAME: Platinol

PHARMACOKINETICS

• ABSORPTION: The drug cisplatin passes through the cell membrane using passive diffusion; where the concentration is higher inside and lower outside, the drug may diffuse directly through the phospholipid layer. The drug cisplatin has high concentration in the liver, kidney, and residual in the bladder, muscle, pancreas, and spleen.
• DISTRIBUTION: Plasma proteins account for 90% of cisplatin bindings, but unlike other drugs, cisplatin binds to plasma proteins in an irreversible process rather than an instantaneous reversible one. Cisplatin becomes cytotoxic in the presence of free platinum.
• METABOLISM: In the liver, cisplatin undergoes non-enzymatic metabolism and changes into proteins, water, and small molecules. It can create inactive complexes when it reacts with glutathione.
• ELIMINATION: Ejected via the kidneys through urine after 24 hrs. A portion of the cisplatin is also expelled through the liver by getting permanently attached to plasma protein (albumin), and also through breast milk. _[14]

HALF-LIFE: Plasma half-life of cisplatin is 30 minutes under IV infusion; it is slowly eliminated with a half-life of 5 days or more. _[14]

PHARMACODYNAMICS: As cisplatin belongs to the class of alkylating agent. It directly binds to the alkyl groups of and stops the cross-link of guanine bases in DNA helix strands, directly attacking DNA. _[14]

DOSE: _[15]

• ADULTS - Cisplatin STANDARD DOSE is 40mg/m² IV WEEKLY
• PEDIATRIC – Cisplatin dose is 60 – 100mg/m² every 3-4 weeks.

CLINICAL INDICATIONS: Cisplatin can be used for various cancers in a similar mechanism of inhibiting tumor cell growth and development., Cisplatin can be used as alone or along with chemoradiation therapy in treating Cervical cancer, Head and neck cancers, Ovarian cancer, Testicular cancer, Bladder cancer, Gastritis cancer, Lung cancer, Esophageal cancer and Others like medulloblastoma, neuroblastoma, penial, anal, osteosarcoma. _[16]

ADVERSE EFFECTS: Cisplatin is irreversibly bound and the most part of the drug is accumulated in the tissues, where it causes serious side effects like;

• Nephrotoxicity – Decreased urine output, lower Mg, K levels, elevated creatinine levels.
• Neurotoxicity – Stroke like episodes, cognitive dysfunction, peripheral neuropathy.
• Ototoxicity – Hearing loss, tinnitus, difficulty in hearing.
• Hepatotoxicity – Jaundice, elevated levels of aminotransferase, decreased levels of albumin in blood.
• Myelosuppression – Neutropenia, anaemia, thrombocytopenia.
• Emetogenic – Severe nausea, vomiting, dehydration, delayed emesis. _[17]

CONTRAINDICATIONS: Possible advantages outweigh the risks, patients with pre-existing renal impairment and hearing impairment should not undergo this treatment.

• Patients with history of hypersensitivity or myelo-suppression should not be given cisplatin. _[18]

DRUG INTERACTIONS:

1. Cisplatin + Doxorubicin

This combination together may increase the risk of side effects like bone marrow or gastrointestinal tract._[19]

2. Cisplatin + Cyclophosphamide

Cyclophosphamide's side effects, particularly bone marrow suppression and stomach/intestinal issues, may worsen when combined with cisplatin or other comparable chemotherapy. Low blood cell counts; infections, anaemia, bleeding, nausea, vomiting, and mouth or abdominal sores are all made more likely as a result. _[20]

3. Cisplatin + Dexamethasone

Using dexamethasone with cisplatin may require dose adjustments or special monitoring. Taking both together can increase the risk of muscle pain or cramps, weakness, dizziness, confusion, and loss of appetite. Inform your doctor promptly if these symptoms occur. _[21]

4. Cisplatin + Paclitaxel

Using cisplatin with paclitaxel can increase the risk of low blood counts, infections, bleeding, anaemia, and nerve damage. Symptoms such as fatigue, unusual bruising or bleeding, fever, flu-like feelings, vision changes, or tingling and numbness in hands or feet should be reported promptly. _[22]

CASE DISCUSSION

Case study 1: (Buccal mucosa)

A patient of 41 yrs male, has been admitted in the oncology department on 11/12/2025 with chief complaints of pain while swallowing, non-healing ulcer, bleeding, pain and numbness. Patient do not have any known history and S/P WLE + MRND + Reconstruction on 07/11/2025.

Upon biopsy it is diagnosed as right buccal mucosa cancer. Now came for treatment and needed investigations done and reports correlated clinically, plan for weekly chemotherapy. On examination the patient is conscious and coherent, Pulse rate-98bpm, Blood pressure-120/80mmhg, Respiratory rate-18/min, Temperature-98.4%, CVS-s1s2+, SP02-99% ra, Lungs- BAE+

On 11/12/2025- WEEK 1 Chemotherapy on CCRT, CISPLATIN- 75mg/ IV in 1 UNIT NS over 2hrs, noted normal parameters

On 18/12/2025- WEEK 2 Chemotherapy on CCRT, CISPLATIN- 70mg/IV in 1 UNIT NS over 2hrs, noted normal parameters

On 26/12/2025- WEEK 3 Chemotherapy on CCRT, CISPLATIN- 70mg/IV in 1 UNIT NS over 2hrs, noted normal parameters

On 02/01/2026- WEEK 4 Chemotherapy on CCRT, CISPLATIN- 70mg/IV in 1 UNIT NS over 2hrs

Laboratory investigations found few abnormal parameters after the 4^th cycle which includes WBC-1800cell/cumm, Potassium-3.0mEq/L, Magnesium-1.0mg/dl, Totalbilirubin1.5mg/dl, Sr. creatinine-1.2mg/dl.

Case Study-2: (Tongue)

A patient of 48 yrs male, has been admitted into the oncology department on 20/11/2025 with chief complaints of painful ulcer, bleeding, pain while chewing and swallowing. Patient has known history of S/P LEFT HEMIGLOSSECTOMY + RND.

Upon laboratory investigations

HISTOPATHOLOGY: Residual viable tumour in the left lateral border of tongue with nodal metastasis and extranodal extension.

PET SCAN: Enhancing liaison involving left lateral border of oral tongue, extending to adjacent floor of mouth

On Examination on time admission the patient is conscious, coherent, Pulserate-98bpm, Blood pressure- 120/80mmhg, Respiratory rate-18/mins, Temperature-98.4F, CVS- s1s2+, Spo2-99%

On 20/11/2025- WEEK 1 Chemotherapy with CCRT, CISPLATIN 70mg/IV in 500ml NS over 3hrs, noted normal parameters

On 27/11/2025- WEEK 2 Chemotherapy with CCRT, CISPLATIN 70mg/IV in 500ml NS over 3hrs, noted normal parameters

On 04/12/2025- WEEK 3 Chemotherapy with CCRT, CISPLATIN 70mg/IV in 500ml NS over 3hrs, noted normal parameters

On 11/12/2025- WEEK 4 Chemotherapy with CCRT, CISPLATIN 65mg/IV in 500ml NS over 2hrs, noted normal parameters

On 19/12/2025- WEEK 5 Chemotherapy with CCRT, CISPLATIN 60mg/IV in 1 UNIT NS over 2hrs

On 26/12/2025- WEEK 6 Chemotherapy with CCRT, CISPLATIN 60mg/IV in 1 UNIT NS over 2hrs

Laboratory investigations found few abnormal parameters from 5^th cycle which include HB- 8.4g/dl, WBC- 2100cells/cumm, Sodium-129mEq/L, Platelets-2.59lakhs/cumm, Urea-32mg/dl.

Case Study-3: (Tongue)

A patient of 46 yrs male, has been admitted into the oncology department on 15/03/2026 with chief complaints of dysphagia with mucositis, difficulty while taking solid food and has known history of cancer of lateral border of tongue, S/P right hemiglossectomy + right neck dissection on 09/01/2026 and has diabetes mellitus type 2 and is on regular medication.

Upon laboratory investigations

MRI IMAGE MORPHOLOGY:

• Heterogeneously enhancing ulcero-nodular altered signal intensity mass lesion along the later margin of the right hemi tongue abutting the lingual cortex of the right maxillary alveolus
• Neoplastic growth, heterogeneously enhancing level IB lymph node on the right side

On Examination on time admission the patient is conscious, coherent, Pulse rate-96bpm, Blood pressure- 140/100mmhg, Respiratory rate-18/mins, Temperature-96.8F, CVS- s1s2+, Spo2-99%

On 15/03/2026 WEEK 1 Chemotherapy with CCRT, CISPLATIN 65mg/IV in 1 UNIT NS over 3hrs, noted normal parameters

On 24/03/2026 WEEK 2 Chemotherapy with CCRT, CISPLATIN 65mg/IV in 1 UNIT NS over 3hrs, noted normal parameters

On 02/04/2026 WEEK 3 Chemotherapy with CCRT, CISPLATIN 55mg/IV in 1 UNIT NS over 3hrs

On 10/04/2026 WEEK 4 Chemotherapy with CCRT, CISPLATIN 55mg/IV in 1 UNIT NS over 3hrs

On 17/04/2026 WEEK 5 Chemotherapy with CCRT, CISPLATIN 50mg/IV in 1 UNIT NS over 3hrs

Laboratory investigations found few abnormal parameters from 3-4^th cycle hence the dose is reduced for following parameters which include WBC-3150cells/cumm, Platelets- 2.02 lakhs/cumm, Sr. creatinine-1.5mg/dl, HB-9.6g/dl

Case Study-4: (Upper lip)

A patient of 39 yrs female, has been admitted into the oncology department on 23/03/2026 with chief complaints of growth over upper lip since 1 month, Pus discharge on & off, evaluated further biopsy done S/P squamous cell carcinoma

Plan: WLE + Free radical flap + right MRND

Upon laboratory investigations

Histopathology: features suggestive of moderately differentiated squamous cell carcinoma grade II

On Examination on time admission the patient is conscious, coherent, Pulse rate-93bpm, Blood pressure- 100/60mmhg, Respiratory rate-18/mins, Temperature-98.4F, CVS- s1s2+, Spo2-98%

On 23/03/2026 WEEK 1 Chemotherapy with CCRT, CISPLATIN 55mg/IV in 1 UNIT NS over 3hrs, noted normal parameters

On 01/04/2026 WEEK 2 Chemotherapy with CCRT, CISPLATIN 55mg/IV in 1 UNIT NS over 3hrs, noted normal parameters

On 08/04/2026 WEEK 3 Chemotherapy with CCRT, CISPLATIN 55mg/IV in 1 UNIT NS over 3hrs, noted normal parameters

On 15/04/2026 WEEK 4 Chemotherapy with CCRT, CISPLATIN 45mg/IV in 1 UNIT NS over 3hrs

Laboratory investigations found few abnormal parameters from 4^th cycle hence the dose is reduced for the following parameters which includes sr. creatinine-1.39mg/dl, HB-10.7g/dl, Platelets- 1.98 lakhs/cumm, WBC-4170cells/cumm.

Case Study-5: (Hard palate)

A patient of 65 yrs female, has been admitted into the oncology department on 23/12/2025 with chief complaints of pain while swallowing and chewing, soreness and has history of Surgery and RT (2018). 

Plan: Weekly chemotherapy with cisplatin along with concurrent radiation therapy.

Upon laboratory investigations

Histopathology: features suggestive of recurrence of well differentiated squamous cell carcinoma, hard palate

On Examination on time admission the patient is conscious, coherent, Pulse rate-87bpm, Blood pressure- 120/70mmhg, Respiratory rate-18/mins, Temperature-98.4F, CVS- s1s2+, Spo2-98%

On 23/12/2025 WEEK 1 Chemotherapy with CCRT, CISPLATIN 60mg/IV in 1 UNIT NS over 3hrs, noted normal parameters

On 31/12/2025 WEEK 2 Chemotherapy with CCRT, CISPLATIN 60mg/IV in 1 UNIT NS over 3hrs, noted normal parameters

On 07/01/2026 WEEK 3 Chemotherapy with CCRT, CISPLATIN 60mg/IV in 1 UNIT NS over 3hrs, noted normal parameters

On 15/01/2026 WEEK 4 Chemotherapy with CCRT, CISPLATIN 55mg/IV in 1 UNIT NS over 3hrs

On 23/01/2026 WEEK 5 Chemotherapy with CCRT, CISPLATIN 50mg/IV in 1 UNIT NS over 3hrs

Laboratory investigations found few abnormal parameters from 4^th cycle hence the dose is reduced for the following parameters which includes sr. creatinine-1.25mg/dl, HB-8.7g/dl, Platelets- 1.25 lakhs/cumm, WBC-2180cells/cumm.

CONCLUSION

Across all five case studies, weekly cisplatin-based concurrent chemoradiation (CCRT) in head-and-neck cancers led to treatment-emergent haematological and biochemical toxicities, requiring close laboratory monitoring and timely cisplatin dose modification to maintain safety without abruptly stopping therapy. This highlights the importance of individualized dosing, early recognition of myelosuppression and renal dysfunction, and balancing treatment intensity with organ protection in oncology practice.

Case study 1 – Buccal mucosa

In the 41-year-old male with right buccal mucosa cancer, weekly cisplatin was tolerated initially, but by the 4th cycle significant leukopenia and electrolyte disturbances (low WBC, potassium, magnesium, and raised bilirubin) were detected, indicating marrow suppression and biochemical toxicity. The case concludes that strict monitoring from early cycles and prompt correction of cytopenias and electrolytes are essential to safely continue cisplatin in buccal mucosa cancers.

Case study 2 – Tongue (residual disease)

In the 48-year-old male with residual tongue tumour and nodal metastasis, extended weekly cisplatin (up to 6 weeks) led to progressive anaemia, leukopenia and hyponatremia from the 5th cycle onward despite initially normal parameters. This case shows that in patients with residual disease and prolonged CCRT, cumulative marrow and electrolyte toxicity becomes a limiting factor, necessitating dose adjustments and supportive care rather than fixed-dose continuation.

Case study 3 – Tongue with diabetes

In the 46-year-old diabetic male with recurrent tongue lesion, MRI confirmed local and nodal disease, and weekly cisplatin caused falling WBC, platelets and rising creatinine from the 3rd to 4th cycles, prompting dose reduction in later weeks. The conclusion is that in comorbid patients (like diabetes with hypertension-range blood pressure), renal and hematologic toxicities appear earlier, making early dose reduction and careful comorbidity control critical to prevent serious complications.

Case study 4 – Upper lip

In the 39-year-old female with moderately differentiated squamous cell carcinoma of the upper lip, weekly cisplatin was initially tolerated, but by the 4th cycle there was a rise in serum creatinine with mild hematologic changes, leading to dose reduction. This case underlines that even in relatively younger patients with apparently stable vitals, cumulative nephrotoxicity can develop after a few cycles, so periodic renal function tests must guide cisplatin dosing.

Case study 5 – Hard palate (recurrent)

In the 65-year-old female with recurrent hard palate carcinoma and prior surgery plus radiotherapy, repeated weekly cisplatin led to creatinine rise and significant anaemia and leukopenia after the 4th cycle, prompting further dose reduction in later cycles. This case concludes that in previously treated and elderly patients, bone marrow reserve and renal reserve are reduced, so maintenance of full-dose weekly cisplatin is rarely feasible beyond a few cycles without toxicity-driven modification.

ACKNOWLEDGEMENT

The authors would like to acknowledge the facilities provided by Bharat Institutions – Pharmacy in executing this article.

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