Cancer Pharm: Immune checkpoint inhibitors + Clinical Application Flashcards
What are the 2 immune checkpoint inhibitors that are PD-1 inhibitors?
Nivolumab and Pembrolizumab
What are the 3 immune checkpoint inhibitors which are PD-L1 inhibitors?
Atezolizumab + Avelumab + Durvalumab
What is the basis for using PD-1 and PD-L1 inhibitors?
- PD-1 is a receptor on T cells
- Tumors express PD-L1; when activated T-cell binds to this receptor it becomes inactivated
What are 4 mechanisms of resistance to immune checkpoint inhibitors (PD-1 and PD-L1)?
- Primary or acquired
- Insufficienct generation of anti-tumor T-cells
- Inadequate function of tumor specific T-cells
- Impaired formation of T cell memory
What are some common and serious AE’s associated with the immune checkpoint inhibitors?
- Fatigue + nausea + loss of apetite + itching
- Serious = immune system attacks normal organs i.e., lungs, intestines, liver, kidneys
Discovery and use of which drug dramatically increased the length of survival in ALL?
Methotrexate
List 4 drugs other than methotrexate which are active against ALL; which 2 drug combo is added to one of these drugs to induce remission?
- 6-mercaptopurine, Cyclophosphamide, Vincristine and Daunorubicin
- Combo of Vincristine + Prednisone + one of the agents from above is used to induce remission
Prednisone is added to anti-tumor regimens due to what 4 effects?
- Inhibits cytokine production
- Alteration of oncogene production
- Cell cycle arrest
- Apoptosis
Which drug/route of administration is used as a prophylactic measure to prevent CNS leukemia in ALL?
Intrathecal methotrexate
What is the most active agent against AML; best used in combo with what drug?
Cytarabine (anti-metabolite) in combo w/ Idarubicin (anthracycline)
After remission is achieved with AML, what is used to maintain durable remission and to induce cure?
- High dose cytarabine
or
- Hematopoietic cell transplantation
What is the standard 1st-line therapy for CML in previously untreated pt’s in the chronic phase?
Imatinib
Which 2 agents are now indicated as 1st-line tx for chronic phase CML, but were originally used in pt’s intolerant/resistant to imatinib?
Dasatinib and Nilotinib
Other than the tyrosine kinase inhibitors (-nib’s) what other agents are effective against CML?
Busulfan and other oral alkylating agents
What are the 2 most widely used alkylating agents for CLL; which non-classic alkylating agent may also be used?
- Chlorambucil and Cyclophosphamide
- May also use Bendamustine
In the tx of CLL, Chlorambucil is often combined with what?
Prednisone
What are the 2 different combo drugs containing Cyclophosphamide used for tx of CLL?
- COP = Cyclophosphamide + Vincristine + Prednisone
- CHOP = Cyclophosphamide + Doxorubicin + Vincristine + Prednisone
Which purine antagonist can be used for CLL as a monotherapy or in combo with what?
- Fludarabine as monotherapy
- Or in combo with cyclophosphamide and with mitoxantrone (anthracycline)
Which 4 drug combo is used in stage I and IIA of Hodgkin’s lymphoma?
ABVD = Doxorubicin + Bleomycin + Vinblastine + Dacarbazine
Which combo drug regimen can be used in advanced stage III and IV Hodgkin’s Lymphoma and is less toxic in regards to infertility and 2’ malignancies?
ABVD = Doxorubicin + Bleomycin + Vinblastine + Dacarbazine
What are the 7 drugs of Standford V regimen for advanced stage III and IV Hodgkin’s Lymphoma?
Doxorubicin + Vinblastine + Mechlorethamine + Vincristine + Bleomycin + Etoposide and prednisone
What is the MOPP combo of 4 drugs that can be used for advanced III and IV Hodgkin’s Lymphoma?
Mechlorethamine + Vincristine + Procarbazine + prednisone
Which 4 combo drug regimen is the best in terms of initial therapy for NHL - diffuse?
CHOP = Cyclophosphamide + Doxorubicin + Vincristine + Prednisone
Which 2 drug combo is used for NHL - nodular (follicular) at the onset of sx’s?
Bendamustine + rituximab
What is the standard 2 drug combo for Multiple Myeloma?
MP protocol = Melphalan (alkylating agent) + prednisone
What are the two drug combos which can be used for stage II breast cancer (each contains 3 drugs)?
- CMF=Cyclophosphamide +Methotrexate +5-Fluorouracil
- FAC = 5-Fluorouracil + Doxorubicin + Cyclophosphamide
What has become the standard 2 drug regimen for hormone refractory prostate cancer?
Docetaxel (works in M phase) + prednisone
Which 2 combos of 3-drug regimens can be used as adjuvant therapy for high risk stage II and II colorectal cancer?
- FOLFOX - folinic acid (leucovorin) + 5-FU + oxaliplatin
- XELOX - capecitabine + oxaliplatin
What is the FOLFIRI regimen for metastatic colorectal cancer; which drug can be added if progression has been observed with oxaliplatin-based chemo?
- FOL-F-IRI - folinic acid (leucovorin) + 5-FU + irinotecan
- Ziv-afilbercept added if progression observed w/ oxaliplatin-based
Using FOLFOX or FOLFIRI with what other drugs results in significantly improved clinical efficacy against metastatic colorectal cancer?
Bevacizumab or cetuximab/panitumab
Which drug has been approved for chemo-refractory metastatic colorectal cancer but has significant toxicities?
TAS-102 (GI toxicity + Neutropenia)
Which adjuvant therapy provides survival benefit in NSCLC in pt’s with pathologic stage IB, II, and IIIA disease?
Platinum-based (-platins)
What is the main drug used in NSCLC in pt’s with good performance status and non-squamous histology; can add which 2 drugs?
Bevacizumab used in combo w/ carboplatin and paclitaxel
If NSCLC pt is not a good candidate for bevacizumab or has a squamous cell histology; which 2 drug combo can be used?
(Cisplatin or Carboplatin) + Cetuximab
Which drug is used as maintenance therapy in NSCLC in pt’s who have stabilized after 4 cycles of platinum based 1st-line tx?
Pemetrexed (active in S phase)
What is 1st line drug for advanced NSCLC pt’s with sensitizing EGFR mutations?
Erlotinib
What is 1st line drug for metastatic NSCLC pt’s with EGFR exon 19 deletions or exon 21 mutations?
Afatinib
Which drug is used for metastatic NSCLC w/ EGFR T790M-mutant following progression on or after EGFR TKI therapy?
Osimertinib (risk of QTc prolongation and cardiomyopathy)
Superior clinical activity against squamous cell NSCLC is achieved when what 3 drug combo used?
Cisplatin and Gemcitabine are combined w/ necitumumab
Which drug is used for squamous cell NSCLC’s that have progressed on or after standard platinum-based chemo?
Nivolumab
What are the two combos of 2-drug regimens which can be used for SCLC that is initially sensitive to platinum-based regimens?
(Cisplatin + etoposide) or (Cisplatin + irinotecan)
What is the 2nd-line monotherapy for SCLC in pt’s that have failed platinum-based regimen?
Topotecan
Along with whole-abdomen radiotherapy what combination (2-drug) tx is used for stage I ovarian cancer?
Cisplatin and Cyclophosphamide
Which 2-drug combo is tx of choice for stage III and IV ovarian cancer?
Carboplatin + Paclitaxel
Which 2 drugs can be used for recurrent ovarian cancer?
Topotecan or liposomal doxorubicin
What is the 3-drug combo used for testicular cancer?
PEB = Cisplatin + Etoposide + Bleomycin
List 2 of the most active cytotoxic agents against Malignant Melanoma?
Dacarbazine and Cisplatin
Which 2 biologic agents have greater activity than cytotoxic agents against Malignant Melanoma?
IFN-α and IL-2
Which 2 drugs are approved for unresectable or metastatic Malignant Melanoma?
Nivolumab and Pembrolizumab
Which nitrosourea can be used as a single agent for brain cancer and what is the 3 drug combo regimen which can also be used?
- Carmustine as single agent
- PCV regimen = Procarbazine + lomustine + Vincristine
Which single drug can be used alone or in combo for glioblastoma multiforme?
Bevacizumab
