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Single Agents
Carboplatin + 5FU
Cisplatin + 5FU
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Carboplatin + Taxol
Cisplatin + Taxol
Overall Treatment Strategy
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HEAD & NECK CANCER SUBTYPES:
Hypopharyngeal Cancer
Laryngeal Cancer
Lip and Oral Cavity Cancer
Metastatic Squamous Neck Cancer with Occult Primary
Nasopharyngeal Cancer
Oropharyngeal Cancer
Paranasal Sinus and Nasal Cavity Cancer
Parathyroid Cancer
Salivary Gland Cancer

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SINGLE AGENTS THAT ARE ACTIVE:
Methotrexate
Cisplatin
5FU
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Carboplatin + 5FU
Carboplatin 400 mg/m2 IV on DAY 1
FLUOROURACIL 5000 mg/m2 CI over 120 hours
Repeat Q21 days

REF:JCO 13:1493, 1995
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CARBOPLATIN + 5FU + XRT (OROPHARYNX)

CARBOPLATIN 70 mg/m2/day X 4
5FU 600 mg/m2/day X 4 (CVI) days 1, 22, 43
XRT 35 fractions (70 Gy)

French Trial. Data presented in abstract. Trial was XRT +/- chemo. 3 year OS 51% vs 31% (P=.002) 3 year DFS 42% vs 19% (p=.003) Locoregional control 66% vs 42%. High grade 3/4 mucositis.

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Cisplatin + 5FU
CISPLATIN 100 mg/m2 IV on DAY 1
FLUOROURACIL 5000 mg/m2 CI over 120 hours
REPEAT Q21 days

REF: JCO 13:1493, 1995
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Paclitaxel + Ifosfamide + MESNA + Cisplatin

PACLITAXEL 175 mg/m2 over 3 hours on DAY 1
IFOSFAMIDE 1000 mg/m2 over 2 hours on DAYS 1-3
MESNA 400 mg/m2 IV before ifosfamide and 200 mg/m2 IV 4 hours after ifosfamide
CISPLATIN 60 mg/m2 IV on DAY 1

REF: JCO 16:1325, 1998

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CARBOPLATIN + TAXOL
3 courses of
paclitaxel 150-265 mg/m2
carboplatin AUC 7.5.
Q 21 days
Those who achieved CR or PR at the primary received definitive XRT to the primary tumor & those with LN disease received neck dissection followed by XRT to the regional LNs.

REF:Cancer 2001 Mar 1;91(5):940-948
N=62; 74% Stage IV; ORR=66%; Responses were observed at all anatomic sites: oropharynx 20 of 33 (61%); hypopharynx 8 of 12 (67%); and larynx 13 of 17 (76%). Organ preservation was achieved in 28 of 62 (45%) of patients at all anatomic sites: oropharynx 39%, hypopharynx 42%, larynx 59%. Seventeen of 28 (61%) patients had their primary organ site preserved for a mean duration of 78 weeks (range, 13-238 weeks).
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CARBOPLATIN + TAXOL (Recurrent)
Paclitaxel 175 mg/m2
Carboplatin AUC 6

REF: Oncology 2001;60(1):66-71
N=27
ORR= 29.6%; median response duration=4.2 months (range 1-5.7 months). Stable & progressive disease = 11.1 & 48.1% of patients, respectively. Median overall survival=7.2 months (range 0.5-10.9 months).
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CISPLATIN + TAXOL

CISPLATIN 75 mg/m2
PACLITAXEL 135 mg/m2 IV over 24 hours

Median surivival 6.8 months. CR 12% (ORR=36%). The stduy was comparing two different doses of taxol. Comparion with Cisplatin+5FU is in progress.

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Common molecular abnormalities:
1. EGF receptor overexpression- 90%
2. P53 mutation 50-70%
3. HPV-16 genome

Overall Treatment Strategy in Head & Neck Cancer:
Stage I/II:
Curative Intent, SINGLE MODALITY THERAPY
Stage III/IV:
Curative intent; MULTIMODALITY THERAPY
Recurrent Disease:
Palliative Care; Investigational Therapies
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MULTIMODALITY THERAPY:

STADNDARD:
Surgery ---> XRT

OTHER APPROACHES:
Induction (neoadjuvant) chemotherapy ---> Surgery ---> XRT
Conurrent Chemoradiotherapy ---> +/- Surgery
XRT--->+/-Surgery

Most studies do NOT show improved SURVIVAL for induction chemotherapy or chemoradiotherapy. However, decreased distant metastasis & organ preservation (i.e. a functional larynx) have been noted.

Currently, there is no role for induction chemotherapy (with cisplatin+ 5FU) except in larynx cancer where it may play a role in organ preservation.

Hyperfractionated XRT has shown a trend in improving survival.