CHEMOTHERAPY IN

ENT
DR.RAJARSHI SANNIGRAHI
JUNIOR RESIDENT
DEPT. OF ENT AND HEAD NECK SURGERY
RG KAR MEDICAL COLLEGE AND HOSPITAL
 INTRODUCTION.
MOST OF STAGE 4 HEAD NECK CANCERS
ARE MANAGED THROUGH CONCURRENT
PLATINUM BASED CHEMORADIATION
ANTI NEOPLASTIC DRUGS COMMONLY
USED IN HEAD NECK CANCERS
PLATINUM COMPOUNDS
CISPLATIN,CARBOPLATIN
NATURAL PRODUCTS
VINKA ALKALOIDS: VINCRISTINE,VINBLASTINE

ANTITUMOUR ANTIBIOTICS: BLEOMYCIN

TAXANES: PACLITAXEL,DOCETAXEL
ANTIMETABOLITES:
FOLIC ACID ANALOGUE: METHOTREXATE
PYRIMIDINE ANALOGUE: 5 FU
DRUGS MODE OF SIGNIFICANT
ACTION ADVERE EFFECTS

VINCA ALKALOIDS INHIBIT POLYMERISATION BONE MARROW

OF MICROTUBULES SUPPRESSION
NEUROTOXIC
SIADH
PLATINUM COMPOUNDS ALKYLATE NUCLEOPHILIC NEPHROTOXIC
BASE MOST COMMONLY OTOTOXIC
N7 OF GUANINE NEUROTOXIC
ASSO. WITH AML
FOLIC ACID ANALOGUE INHIBIT DHFR BONE MARROW
SUPPRESSION
INHIBIT THYMIDYLATE
SYNTHATASE
PYRIMIDINE 5 FU 5 dUMP HAND AND FOOT
ANALOGUE SYNDOME
INHIBIT THYMIDYLATE NEUROTOXICITY
SYNTHETASE
ANTITUMOUR DNA STRAND BREAKAGE CUTANEOUS TOXICITY
ANTIBIOTICS VIA FREE RADICAL
FORMATION
 MODE OF USE OF
CHEMOTHERAPY
NEOADJUVANT (INDUCTION)

CONCURRENT(CONCOMITANT)

ADJUVANT(POST OPERATIVE)

PALLIATIVE
NEOADJUVANT CHEMOTHERAPY
ITS THE USE OF CHEMOTHERAPY PRIOR TO DEFINITIVE
SURGERY OR RADIATION

THE INTENTS OF USING CHEMOTHERAPY ARE

LOCAL CONTOL OF DISEASE
CONTOL OF DISTANT METASTASIS
GREATER ORGAN PRESERVATION

AS THERE ARE NO VASCULAR DAMAGE WITH PREVIOUS

SURGERY OR RADIOTHERAPY SO THIS TYPE OF
CHEMOTHERAPY SHOULD BE MORE EFFECTIVE
 CONTINUE.
DOSE SCHEDULE OF NEOADJUVANT
CHEMOTHERAPY
CISPLATIN+5 FU(PF)
DAY 1:CISPLATIN 100mg/m2
+

Day 1-5:5 FU iv infusion 1000mg/m2

Repeat every 3 wks for 4cycles
 International trials for
neoadjuvant chemotherapy
VA TRIAL NO.268 CT-RT VS SURG RT(P)
EORTC TRIAL IN EARLY 90S

INTERGROUP TRIAL 91-11(PF)

PIGNON METAANALYSIS

ALL THESE STUDIES SHOWED

The addition of chemotherapy reduced distant
metastasis and improves disease free survival
BUT.it also concludes
CONCURRENT THERAPY IS SUPERIOR TO
INDUCTION THERAPY
 RENEWED INTEREST IN
NEOADJUVANT CHEMOTHERAPY
WITH ADITION OF TAXANES THE NEOADJUVANT
CHEMOTHERAPY SHOWS SIGNIFICANT
IMPROVEMENT IN

1. INCREASE RESPONSE TO CHEMOTHERAPY

2. INCREASE IN SURVIVAL
3. DECREASE INCIDENCE OF THROMBOCYTOPENIA
4. INCREASE IN ORGAN PRESERVATION
 DOSE SCHEDULE

DOCETAXEL+CISPLATIN+5 FU DAY 1:DOCETAXEL 75mg/m2 and

(TPF) CISPLATIN 750mg/m2
DAY 1-5:5 FU 750mg/m2

Repeat every 3 wks for 4 cycles

CONCURRENT CHEMOTHERAPY

WHEN RADIOTHERAPY AND

CHEMOTHERAPY ARE USED
SIMULTANEOUSLY
INTENT IS SYSTEMIC CONTROL THROUGH
ELIMINATION OF MICRO-METASTASES
AND IMPROVED LOCAL CONTROL BASED
ON THE CONCEPTS OF ADDITIVITY AND
SYNERGY
 RADIOBIOLOGICAL RATIONALE
FOR THE SYNERGISTIC USE
CHEMOTHERAPY AIDS TO RADIOTHERAPY AIDS TO
RADIOTHERAPY VIA.. CHEMOTHERAPY VIA.

1.INHIBITING THE SUBLETHAL 1.INHIBITING DNA REPAIR

DNA DAMAGE REPAIR

2.REDUCTION IN TUMOUR 2.DECREASE TUMOUR MASS SO

CLONOGEN REPOPULATION INCREASED BLOOD DELIVERY TO
TUMOUR WHICH FAVOURS
3.KILLING RADIORESISTANT CHEMOTHERAPY
HYPOXIC CELLS

4.REDUCE TUMOUR BULK WHICH

HELPS IN REOXYGENATION
 DOSE SCHEDULE
CISPLATIN DAYS 1,22 AND 43:CISPLATIN
100mg/m2 iv+CONCURRENT
RADIOTHERAPY 2Gy/DAY TO
TOTAL 70 Gy

CARBOPLATIN +INFUSIONAL 5 FU DAYS 1-4:5 FU 600mg/m2/day AS

CONTINUOUS IV INFUSION
+CARBOPLATIN 70mg/m2/day IV
BOLUS.
REPEAT EVERY 3 WKS FOR 3
CYCLES WITH CONCURRENT
RADIOTHERAPY
ADJUVANT CHEMOTHERAPY
FOLLOWING DEFINITIVE SURGERY WHEN
CHEMOTHERAPY IS USED
ADJUVANT CONCURRENT CHEMORADIATION IS
THE PRESENT MODALITY
PRESENCE OF
1.INADEQUATE RESECTION MARGINS
2.EXTRA NODAL SPREAD
3.PERINEURAL SPREAD
4.LYMPHOVASCULAR INVASION
CAN BE ADDRESSED WITH.
 PALLIATIVE
CHEMOTHERAPY
CISPLATIN AND 5 FU REMAINS THE
STANDARD MODE OF TREATMENT
 CURRENT STATUS OF
CHEMOTHERAPY IN
NASOPHARYNGEAL CA
COMBINED INDUCTION AND
CONCURRENT CHEMORADIOTHERAPY IN
ADVANCED STAGE
NASOPHARYNGEALCA
EXCELLENT TUMOUR SHRINKAGE PRIOR
TO RADIOTHERAPY
 TARGET THERAPIES
DRUG MODE OF ACTION USE

1.IM-C225 ANTIBODY TO EGFR HNSCC

CETUXIMAB

2. FARNESYL TRANSFERASE DECREASE ORAL CAVITY

INHIBITOR TUMOUR BULK

3.AD-p53 p53 DECREASE RECURRENCE

OF HNSCC

4.RENINOIDS RETINOIC ACID DECREASE LEUCOPLAKIA

5.SULINDAC COX 2 INHIBITOR HNSCC

CELECOXIB
 DRUGS USED TO PREVENT
CHEMOTHERY INDUCED
DRUG
TOXICITY INDICATIONS
MECHANISM
1.APREPITANT NK 1 ANTAGONIST CISPLATIN INDUCED VOMITING

2.RASBURICASE RECOMBINANT URATE OXIDASE PREVENT HYPERURICAEMIA FROM

TUMOUR LYSIS
3.LEUCOVORIN REPLETE TETRAHYDROFOLIC ACID RESCUE AFTER HIGH DOSE
METHOTREXATE
4.AMIFOSTINE PREVENTS XEROSTOMIA AND
NEPHROTOXICITY
5.PALIFERMIN KERATINOCYTE GROWTH FACTOR PREVENTS MUCOSITIS
6.PILOCARPINE CHOLINERGIC AGONIST RADIATION INDUCED XEROSTOMIA
7.PAMIDRONATE BISPHOSPHONATES HYPERCALCAEMIA IN
MALIGNANCY
8.EPOETIN-ALFA ERYTHROPOETIN ANAEMIA
9.FILGRASTIM G-CSF FEBRILE NEUTROPENIA
PROPHYLAXIS
10.OPRELVEKIN IL 11 THROMOCYTOPENIA