1. Chemotherapy of malignant tumors
Ewa Chmielowska

2. Intraductory remarks
Indication to carry out an anticancer CHT should only be made by a specialized oncologist
And should only be realized under the supervision of and trained staff
Qualification, monitoring ,
Safety/effective treatment

3. Chemotherapy - What is this ?
Chemotherapeutic agent are focused on killing rapidly proliferating cancer cells
Target – cellular metabolic process including DNA, RNA and protein biosynthesis
Not specific for cancer cells
New type of CHT is termed targeted therapy. These are biologic agents more specific for cancer cells ( signal transduction and cellular signalling stop)

4. The history Chemotherapy have been known since the 1950s
Alkylating( CTX) ,antimetabolites:antifolates( MTX, Cytosar)fluoropirymidines( FU), microtubules agents( VCR)
Topoisomerase interactive agents: TPT, Camto,Vp
Antracyclines
Cisplatin and analogues
Taxanes

5. Biotherapeutics Interferons: recombinant alfa 2 Interleukin-2
Ipilimumab
nivolumab

6. Old targeted anticancer drug= endocrine manipulation
Breast cancer:
selective estrogen receptor modulator – Tamoxifen,raloxifen, fulvestrant
Medroksyprogesterone
Aromatase inhibitors steroidal and nonsteroidal – blocked estrogen synthesis via conversion of the androgen and testosteron in post menopausal women
LHRH analogs

7. Endocrine amnipulation
Prostate cancer:
LHRH analogs-
Antiandrogens – flutamid( treatment combined with GnRH analog)
Bicalutamid -nonsteroidal antiandrogen binding receptor 4 times more than flutamid
Lastly: abiraterone, enzalutamid

8. New Targeted Anticancer Drug
Histone Deacetylase Inhibitors( HDACs) – enzyme involved in epigenetic gene regulation
Monoclonal antibody (Mabs) mouse, human: rituximab, trastuzumab, alemtuzumab, ibritumomab tiuxetan, bevacyzumab, cetuximab, panitumumab
TKI inhibitors: gefitinib, erlotinib
M-TOR inhibitors: everolimus, temsirolimus

9. Dose calculation and modification
Dose is calculated on the basis of the individual body surface area, sometimes on the basis of the patient weight, or on renal function(AUC)
Dose modifications are indicated in dependence of the toxicity- hematologic or others – reduction or delay – CTC criteria
Maximal dose( individual or cumulative) should not to be exceeded: eg ADB, BLEO

10. Metronomic chemotherapy
Chronic administration
Low dose at close regular intervals
No prolonged drug free interruptions
Lower toxicity
Reduced risk of drug resistant tumor cells
Antiangiogenic activity

11. Special pre and co-medication -examples
To redue risk of hypersensivity ( taxanes, pegylated doxorubicin) – dexamethasone
Monitoring the blood level of drug ( MTX, FU)
Folinic acid to rescue HD MTX
Mesna- uroprotective agent ( HD CTX, Ifosfamid)
To reduce risk of nephrotoxicity ( cispatinum) hydratation 0,9 % Saline minimum 1000 ml

12. Chemotherapy – steps in drug development
Drug candidate selection via pharmacology
Production and formulation
Safety assesssment – toxicology
Phase I clinical trials
Phase II
Phase III-IV
Approval via FDA , EMA
General Medical practice

13. What we should know
Pharmacokinetics and pharmacodynamics of the drug– concentration-response relationships: bioavailability, volumes of distribution, protein binding free, drug concentration, clearance, elimination half time, dose proportionality
Mechanism of resistance

14. Practice informations
Treatment plan is based on:
1.pathomorphologic diagnosis ( includes IHC or genetic evaluation)
2.TNM staiging ( any necessairy lab, CT scans, endoscopy)
3. all informations about concomitant diseases
4. toxicity profile of agents
5. patients prefernce

15. Type of therapy Radical Palliative Best supportive care
Remission induction
Maintenance
Consolidation

16. What we should done during treatment
Control the efficacy ( CR, PR, SD, PD)
Control the toxicity
Differentiate between symptoms of progression and others comorbidities
Remember about roules of combined modality treatment ( with surgery, radiotherapy)

17. Homework Group 1: breast cancer and ovarian cancer
Group 2: lung cancer and colon cancer
Questions :
1 .Clinical course of disease
2. Main rules of treatment