Chemo basic Flashcards
Gompertzian tumor growth
pattern of exponential growth with exponential growth retardation.
What are the 3 cell growth types?
1) Static – neurons, striated muscle, oocytes
2) Expanding (normally quiescent except under stress/injury a proliferative burst is followed by return to quiescence)- hepatocytes, bile duct epithelium, vascular endothelium
3) Renewing (continuous proliferation) – bone marrow, epithelium, GI epithelium, sperm
Tumor doubling curve
-As tumor mass increases the time to double the tumor volume decreases.
-At later stages of tumor growth a small # of doublings produce a marked change in tumor size w/ increased potential for adverse clinical consequences.
-In general metastases have faster doubling times than their corresponding primary lesions.
Average doubling time for human cancers is 50 days.
1 cm mass ~ X number of doubling
30
Growth Fraction
The proportion of tumor cells that are actively cycling.
Usually those cells near small blood vessels.
Variable by tumor type – 25-95%
Cell loss in tumors is high…70-95%
First order Cell Kill Kinetics
A constant fraction of exposed cells are killed, rather than a constant number.
For curative chemotherapy, log cell kill (% of cells killed each cycle) must be very large (>99%) and repetitive.
Cure or prolonged survival achieved when…
cell pop reduced to 10 ^1 and 10^ 4 (not clinically detectable.
Hepatic metabolism (ICE VAT)
If you don’t take the liver into account, you’ll need an ice vat
- Vinca alkaloids (vincristine, vinblastine, vinorelbine)
- Ifos, Cytoxan, etoposide (hepatically metabolized, renally cleared)
- Taxanes (Taxol, Taxotere)
- Anthracycylines (doxil, doxorubicin)
- VEGF inhibitors (cleared)
- dose reduce MTX bc can cause hepatic fibrosis (Renault cleared)
- 5 FU
Renal clearance (Top BMI Promotes Cancer)
Platinums Bleomycin MTX Topotecan Ifos Cytoxan
Alkylating agents (contain + charged alkyl groups that bind neg charged DNA)
- Direct DNA damage (X-link, free radical, strand breakage) G1, S, G2 arrest
- RT, platinum
- Nitrogen mustards(cytoxan, ifos, melphalan)
- Temodar
- Bleomycin (not exactly alkylating agent, produces ROS-> DNA breaks)
Antimetabolites
- Inhibition of nucleotide synthesis. G1, S arrest
- Antifolates(MTX, pemextred), nucleoside analogs (5FU, gemzar), hydroxyurea
Microtubule
M arrest
Taxanes (taxol, doxetaxol) promote tubulin polymerization
Vinka alkaloid inhibit polymerization
Topoisomerases
- Topo II inhibitors :anthracyclines (doxorubicin, doxil),etoposide, actinomysin D
- Topo I inhibitors: Topotecan
- S phase
Signal transduction
- Growth factor blockade: Trastuzumab, cetuximab, bevicizumab, pertuzumab
- Inhibition of Tyr kinase signal transduction: erlotinib, gefitinib, imitanib, sorafenib, sunitinib, lopatinib
- Hormonal inhibition
RECIST = Response Evaluation Criteria in Solid Tumors
At least one 2cm (one dimension) target lesion
Other non target lesions
CR – disappearance of all target & nontarget
PR – disappearance of all target, without progression of nontarget & no new, at least 30% decrease in sum LD
PD – 20 % increase sum LD of targets
SD – BTWN PR and PD
CR: complete response, PR: partial response, LD: longest diameter, PD: progressive disease, SD: stable disease
Bone Marrow Toxicity
- Neutropenia #1 manifesting 7-14 days from tx, lasting 3-10 days
- RT, alkylating agents,DNA damaging agents (nitrosoureas, mitomycin C) can have cumulative effects
Emetogenicity
High: Cisplatin, carboplatin, Cytoxan, dactinomycin
Low: Bleomycin, taxanes, vinca alkaloids, 5FU, MTX, doxil, gemzar, topotecan
Which chemotherapies cause Alopecia?
TEA CUP
Worst: Taxanes, doxorubicin/doxil, IV etoposide
Possible: platinums, Cytoxan, 5FU
Which chemotherapies cause Neurotoxicity?
Cisplatin*, taxanes, hexalen,
-cisplatin sx’s come on later and continue after stopping tx
What dugs cause PPE?
Oral etoposide, 5 FU, Doxil, bleomycin, docetaxel, MTX
FU Doxil Making Beautiful Toes Erythematous
Which chemotherapies are vesicants (can cause extravasion necrosis)?
Doxorubicin, dactinomycin, Taxotere, vincristine, mitomycin C
Genitourinary complication of chemotherapy
- Cisplatin: AKI if UOP not maintained. Mg and K loss known
- Hemorrhagic cystitis: Ifos-use mesna to bind acrolein. Can also happen with cytoxan
What EXACTLY is cremephor??
- Carrier of paclitaxel
- Mixture of polyoxyethylated castor oil and dehydrated alcohol (leads to mast cell degranulation and clinical HSR)
Timing of hypersensitivity reactions
- Platinum: second cycle of second course (~eighth)
- Taxol: 1st or 2nd cycle
