Chemoradiation Flashcards
1
Q
What are the current evidence based indications for chemotherapy in the MAN of HNC?
A
- Organ preservation of larynx (resectable stage III and IV dz, excluding T1): RT 70 Gy + high dose cisplatin
- Organ preservation of hypopharynx (resectable stage III and IV dz, excluding T1): Cisplatin + 5-FU x 3 cycles, then 70 Gy RT
- Oropharynx, resectable T3-T4 or N2-N3: RT 70 Gy + cisplatin or carboplatin + 5-FU x 3 cycles
- NP stages IIB, III, IVA, IVB: RT 70 Gy + high dose cisplatin, adjuvant cisplatin + 5-FU x 3 cycles
- Unresectable, all sites: RT 70 Gy + cisplatin
- Postop adjuvant (ECS or + margins): 70 Gy RT + high dose cisplatin
- CI to systemic chemo, stage III or IV dz: Cetuximab followed by 70 Gy RT + cetuximab
2
Q
Chemotherapy effects
A
- Enhance effects of RT
- Shrink tumors
- Not curative
- May not reach center of tumor
3
Q
What is more effective:
- Induction chemo then RT or
- Concurrent chemoRT
A
Concurrent chemoRT is more effective but more severe SE (mucositis, swallowing difficulties)
4
Q
What are the most commonly used cytotoxic drugs used to treat recurrent or metastatic HNSCC
A
- Cisplatin
- Carboplatin
- Docetaxel
- Paclitaxel
- 5-FU
- MTX
- Cetuximab
5
Q
Cisplatin
A
- Platinum-based alkylating agent
- Covalent adducts w/ DNA that block replication and transcription
- Tox: renal, GI, myelosuprression, oto, peripheral neuropathy, visual, sz’s
- HL from loss of outer hair cells via R.O.S.
6
Q
Carboplatin
A
- Lower rates of nephro and neurotox
- Less N/V
7
Q
5-FU
A
- Inhibits DNA synthesis by binding thymidylate synthase w/ subsequent depletion of precursor proteins for DNA synthesis
- S phase
- SE: BM suppression, GI mucositis, hyperpigmentation, dermatitis, alopecia, conjunctivitis, blepharitis, epiphora
- Synergistic w/ other chemo drugs and RT
8
Q
Docetaxel
A
- Taxane
- Target mitosis by binding microtubules, stabilizing them and disrupting microtubule dynamics thus inhibiting spindle fnc
- Induce mitotic arrest then apoptosis
- Tox: myelosuprresion w/ neutropenia, hair loss, fluid retention
9
Q
Paclitaxel
A
- Taxane
- Peripheral neuropathy and arthralgia
10
Q
Methotrexate
A
- Antifolate antimetabolite
- Inhibition of dihydrofolate reductase
- Prevents nl thymidylate and purine nucleotide synthesis resulting in single and ds DNA breaks
- S phase
- Tox: myelosuppression, GI mucositis, nephrotox, hepatotox, neurotox, acute/chronic hepatic dysfnc, encephalopathy, dementia
11
Q
What are biologic modifiers for HNC?
A
Basically all target EGFR
- Cetuximab (monoclonal Ab to EGFR)
- Panitumumab (same)
- Gefitinib (TK inhibitors (downstream of EGFR))
- Erlotinib (same)
12
Q
What is the main SE of cetuximab?
A
Acneiform rash in 84% (a good sign for prognosis)
13
Q
What are the different administration schedules of chemo?
A
- Induction (neoadjuvant) chemo
- Concurrent chemoRT
- Sequential (induction then concurrent)
- Adjuvant chemo
14
Q
What are the general ways chemo is used in HNC?
A
- Organ preservation (use w/ RT)
- Locally advanced, unresectable dz
- Post-op for high risk dz (w/ RT)
- Palliation of recurrent, inoperable dz
15
Q
Studies re: organ preservation of the larynx
A
- VA Laryngeal Cancer Study Group 1991
- 64% of advanced larynx CA pts preserved their larynx w/ chemoRT
- More chemoRT failed locally but less distantly vs surgery
- Less second primaries in the chemoRT group vs surgery
- Salvage surg predictors: T4 and Stage IV dz
- RTOG 91-11 study
- 3 arms: induction cisplatin & 5-FU then RT; concurrent cisplatin/RT; RT alone
- overall survival similar
- locoregional control better in concurrent group
- 2 yr laryngeal preservation rate better in concurrent group
- Concurrent group required less salvage TL’s
