Pembrolizumab, Carboplatin and 5-Fluorouracil Treatment Protocol for Head and Neck Cancer

ContributorsProf. Dr. Mustafa ÖzdoğanAuthor · Medical review · Editorial approval

PublishedJul 16, 2025

UpdatedOct 17, 2026

5 min read

Pembrolizumab, Carboplatin and 5-Fluorouracil Treatment Protocol for Head and Neck Cancer

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Pembrolizumab, Carboplatin and 5-Fluorouracil Protocol for Head and Neck Cancer

Head and neck squamous cell carcinoma (HNSCC) is one of the most challenging cancers to manage, particularly when it recurs or spreads through the body (metastasis). For many years, chemotherapy was our only option, and survival was unfortunately limited.

However, the “immunotherapy revolution” in oncology changed this bleak outlook. Following the results of the landmark KEYNOTE-048 trial, the combination of immune-boosting Pembrolizumab (a targeted drug) with standard chemotherapies (Carboplatin and 5-FU) offered new hope for eligible patients.

This protocol aims not only to shrink the tumor, but also to train the immune system for a sustained fight against cancer. In this article, we will examine all the details of this powerful triple therapy, which is also reimbursed in Türkiye, including who receives it, how it is administered and what requires attention.

Drug Glossary:

Pembrolizumab (Keytruda®): An immunotherapy that blocks the tumor’s “brake” mechanism (PD-1). It prevents cancer cells from hiding from the immune system and allows T cells to attack the tumor.

Carboplatin: A platinum chemotherapy drug. By linking DNA strands together, it makes cancer cell division impossible and leads to cell death.

5-Fluorouracil (5-FU): An “antimetabolite” that disrupts DNA and RNA synthesis in cancer cells. It is usually given slowly through a pump over 4 days.

PD-L1 and CPS Score: A test indicating how well the tumor will respond to immunotherapy. This treatment requires PD-L1 positivity (CPS ≥1) in the patient’s tumor.

The Rationale: Why Three Drugs Together?

This treatment protocol is based on a “Hit and Reveal” strategy. Chemotherapy and immunotherapy strengthen each other’s effects (synergy).

1. Chemotherapy (Carboplatin + 5-FU): It breaks down rapidly dividing tumor cells. During this process, “tumor antigens” (the tumor’s identity cards) are released from the disintegrating tumor into the surrounding area.

2. The “Hot” Tumor Effect: A tumor that normally goes unnoticed by the immune system (“cold”) becomes visible (“hot”) through the stress and inflammation caused by chemotherapy.

3. Immunotherapy (Pembrolizumab): It enters the scene and releases the suppression of T cells. The already-stimulated immune system then attacks the vulnerable cancer cells much more strongly.

SGK Reimbursement Status in Türkiye

As of July 10, 2025, Pembrolizumab for head and neck cancers is covered by the state when the following conditions are met:

Metastatic disease or inoperable (unresectable) recurrent disease.
A diagnosis of head and neck squamous cell carcinoma.
PD-L1 CPS Score ≥ 1 is required.
Good patient performance status (ECOG PS 0-1).
No previous systemic treatment (or at least 6 months since curative treatment).
Repeat use is not reimbursed in patients who have previously received immunotherapy.

How Is Treatment Administered?

This treatment usually involves a day admission to hospital followed by continuation at home.

Drug	Administration	Frequency
Pembrolizumab	Intravenous infusion (IV) - Approximately 30 minutes	Every 3 weeks (or every 6 weeks depending on the dose)
Carboplatin	Intravenous infusion (IV) - Day 1	Every 3 weeks
5-Fluorouracil (5-FU)	First a short loading administration, followed by a slow infusion lasting 96 hours (4 days) . *The patient is usually sent home with a portable pump or an elastomeric “bottle” pump.	Every 3 weeks

*Usually given with 4-6 cycles of chemotherapy, followed by Pembrolizumab alone for up to 2 years.

Who Cannot Receive This Treatment? (Contraindications)

Active Autoimmune Diseases: In diseases such as Lupus, Rheumatoid Arthritis and Crohn’s disease, the immune system is already attacking the body. Immunotherapy may make this situation fatal.
Severe Organ Failure: Patients with impaired kidney and liver function cannot tolerate this intensive treatment (particularly Carboplatin and 5-FU).
Poor Performance Status (ECOG 3-4): This treatment may be too demanding for patients who are bedridden or unable to care for themselves.
Active Infections: Treatment is risky in the presence of uncontrolled Hepatitis or HIV.

Side Effects: What Should You Prepare For?

Two different groups of side effects may occur with this treatment: chemotherapy-related and immunotherapy-related effects.

Low Blood Counts: Anemia (58%), Leukopenia (34%). Increases infection risk.
Gastrointestinal: Nausea (51%), Vomiting, Diarrhea, Mouth sores (Mucositis).
Weakness and Fatigue: One of the most common complaints.
Hand–Foot Syndrome: Redness/peeling of the palms and soles (caused by 5-FU).

These occur when the immune system attacks healthy tissues (less common, but serious).

Thyroid Disorders: Hypothyroidism (16%).
Pneumonitis: Immune-related lung inflammation (Cough, shortness of breath).
Colitis: Severe diarrhea and abdominal pain.
Hepatitis: Elevated liver enzymes.
Skin Rashes: Itchy rashes.

DROZDOGAN Academy Commentary

Head and neck cancers affect some of the areas most closely connected to a patient’s daily life, so their treatment requires great care. The Pembrolizumab, Carboplatin and 5-FU combination (KEYNOTE-048 Protocol) is one of our most powerful tools, particularly in metastatic or recurrent disease.

However, we must remember: “Not every drug is suitable for every patient.” The success of this treatment depends on appropriate patient selection (PD-L1 positivity, good performance status) and very careful management of side effects. In particular, 5-FU-related cardiac problems and hidden immunotherapy-related inflammation (such as pneumonitis) must not be overlooked.

Its inclusion in SGK reimbursement is a major opportunity for our patients. This treatment can not only extend life, but also preserve quality of life when managed properly.

References:

Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. The Lancet. 2019.
SGK Sağlık Uygulama Tebliği (SUT) Değişiklikleri ve Geri Ödeme Listesi, 10 Temmuz 2025.

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Pembrolizumab, Carboplatin and 5-Fluorouracil Treatment Protocol for Head and Neck Cancer