This document provides chemotherapy protocols for treating non-small cell lung cancer (NSCLC) at different stages. It outlines adjuvant chemotherapy regimens for stage I-II NSCLC using platinum-based doublets. For stage III disease, it recommends concurrent chemotherapy and radiation therapy followed by consolidation therapy. First-line treatment options for stage IV or recurrent disease include platinum-based doublets or single-agent therapy. It also provides recommendations for EGFR/ALK mutation-positive tumors and tumors with high PD-L1 expression. Guidelines are given for second-line and third-line chemotherapy, as well as maintenance options and targeted therapies.

1. CHEMOTHERAPY
PROTOCOL OF NSCLC
Presented By:
FARUK HOSSAIN

2. ADJUVANT CHEMOTHERAPY
PROTOCOL
STAGE I OR II NSCLC
With chemotherapy for stage I or II NSCLC, the goal is to complete four cycles. Acceptable
adjuvant chemotherapy regimens include the following:
Cisplatin 50 mg/m 2 IV on days 1 and 8 plus vinorelbine 25 mg/m 2 IV on days 1, 8, 15, and 22
every 28 d or
Cisplatin 100 mg/m 2 IV on day 1 plus vinorelbine 30 mg/m 2 on days 1, 8, 15, and 22 every 28
d or
Cisplatin 75-80 mg/m 2 IV on day 1 plus vinorelbine 25-30 mg/m 2 IV on days 1 and 8 every 21
d or
Cisplatin 100 mg/m 2 IV on day 1 plus etoposide 100 mg/m 2 IV on days 1-3 every 28 d or
Cisplatin 80 mg/m 2 IV on days 1, 22, 43, and 64 plus vinblastine 4 mg/m 2 IV on days 1, 8, 15,
22, and 29; then every 2 wk after day 43 until completion of cisplatin every 21 d or
Cisplatin 75 mg/m 2 IV on day 1 plus gemcitabine 1250 mg/m 2 on days 1 and 8 every 21 d or
Cisplatin 75 mg/m 2 IV on day 1 plus docetaxel 75 mg/m 2 IV on day 1 every 21 d or

3. PATIENTS NOT ABLE TO TOLERATE
CISPLATIN MAY ALTERNATIVELY USE
THE FOLLOWING REGIMEN:
Carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m 2 IV on day 1 every 21 d
(see the Carboplatin AUC Dose Calculation [Calvert formula] calculator)
https://reference.medscape.com/calculator/carboplatin-auc-dose-calvert

4. CONCURRENT
CHEMOTHERAPY/RADIATION THERAPY
REGIMENS
Following concurrent chemotherapy and radiation therapy, National Comprehensive Cancer Network
guidelines recommend consolidation therapy with durvalumab for stage III disease.
Acceptable chemotherapy regimens for use in concurrent chemotherapy/radiation
therapy are as follows:
Cisplatin 50 mg/m 2 IV on days 1, 8, 29, and 36 plus etoposide 50 mg/m 2 IV on days
1-5 and days 29-33 or
Cisplatin 100 mg/m 2 IV on days 1 and 29 plus vinblastine 5 mg/m 2/weekly IV for 5
wk or
Carboplatin AUC 2 IV weekly for 7 wk plus paclitaxel 50 mg/m 2 IV weekly for 7 wk; 3
wk later, it can be followed by two cycles of consolidation chemotherapy with
carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m 2IV on day 1 every 21 wk or
Carboplatin AUC 5 IV on day 1 plus pemetrexed 500 mg/m 2 IV on day 1 every 21 d for

5. FIRST-LINE CHEMOTHERAPY,
METASTATIC OR RECURRENT DISEASE
STAGE IV OR RECURRENT DISEASE
Patients with metastatic disease (stage IV) or recurrent disease after primary therapy (eg, surgery and/or radiation) should be
considered for chemotherapy in order to improve quality of life, palliate symptoms, and improve overall survival. [11, 7]The goal is
to treat for four to six cycles unless otherwise specified.
Chemotherapy regimens, including platinum-based doublets, are as follows:
Cisplatin 75 mg/m 2 IV on day 1 plus paclitaxel 175 mg/m 2 IV on day 1 every 21 d or
Cisplatin 100 mg/m 2 IV on day 1 plus gemcitabine 1000 mg/m 2 IV on days 1, 8, and 15 every 28 d or
Cisplatin 60 mg/m 2 IV on day 1 plus gemcitabine 1000 mg/m 2 IV on days 1 and 8 every 21 d or
Cisplatin 75 mg/m 2 IV on day 1 plus docetaxel 75 mg/m 2 IV on day 1 every 21 d or
Carboplatin AUC 6 IV on day 1 plus paclitaxel 175-225 mg/m 2 IV on day 1 every 21 d or
Carboplatin AUC 6 IV on day 1 plus paclitaxel 90 mg/m 2 IV on days 1, 8, and 15 every 28 d or
Paclitaxel protein bound 100 mg/m2 IV on days 1, 8, and 15 of every 21 d plus carboplatin AUC 6 IV on day 1 or
Carboplatin AUC 6 IV on day 1 plus docetaxel 75 mg/m 2 IV on day 1 every 21 d or
Carboplatin AUC 5 IV on day 1 plus gemcitabine 1250 mg/m 2 IV on days 1 and 8 every 21 d or
Cisplatin 100 mg/m 2 IV on day 1 every 28 d plus vinorelbine 25 mg/m 2 IV weekly or
Cisplatin 40 mg/m 2 IV on day 1 plus vinorelbine 25 mg/m 2 IV on days 1 and 8 every 21 d or
Carboplatin AUC 5 IV on day 1 plus vinorelbine 30 mg/m 2 IV on days 1 and 8 every 21 d

6. TREATMENT RECOMMENDATIONS FOR
TUMORS WITH EPIDERMAL GROWTH
FACTOR RECEPTOR (EGFR)
IMMUNOHISTOCHEMISTRY ARE AS
FOLLOWS:Cisplatin 80 mg/m 2 IV on day 1 plus vinorelbine 25 mg/m 2 IV on days 1 and 8 plus cetuximab 400 mg/m 2 IV
loading dose, followed by 250 mg/m 2 IV weekly every 21 d (continue cetuximab weekly after four to six cycles
completed, until disease progression)
Erlotinib, afatinib, and gefitinib are approved by FDA for first-line treatment of metastatic NSCLC in patients
whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-
approved test, such as the cobas EGFR mutation test and therascreen EGFR RGQ PCR Kit. Treatment
recommendations include the following:
Erlotinib 150 mg PO daily until disease progression
Afatinib 40 mg PO daily until disease progression
Gefitinib 250 mg PO daily until disease progression
Treatment recommendations for anaplastic lymphoma kinase (ALK)–positive locally advanced or metastatic
tumors are as follows:
Crizotinib 250 mg PO BID until disease progression; dosing interruption and/or dose reduction to 200 mg PO BID
may be required, based on safety and tolerability; decrease to 250 mg PO daily if further reduction is needed OR
Ceritinib 750 mg PO daily until disease progression; dosing interruption and/or dose reduction may be required
based on safety and tolerability
Crizotinib resistance/intolerance: Alectinib 600 mg PO BID until disease progression; dosing interruption and/or

7. Pembrolizumab can be used as a single-agent first-line for tumors with high PD-L1
expression [Tumor Proportion Score (TPS) ≥50%)] as determined by an FDA-approved
test, with no EGFR or ALK genomic tumor aberrations are as follows:
Pembrolizumab 200 mg IV q3wk until disease progression or unacceptable toxicity, or
up to 24 months in patients without disease progression

8. TREATMENT RECOMMENDATIONS FOR
PATIENTS WITH CONTRAINDICATIONS
TO CARBOPLATIN OR CISPLATIN ARE
AS FOLLOWS:
Gemcitabine 1100 mg/m 2 IV on days 1 and 8 plus docetaxel 100 mg/m 2 IV on day 8
every 21 d or
Gemcitabine 1000-1200 mg/m 2 IV on days 1 and 8 plus vinorelbine 25-30 mg/m 2 IV
on days 1 and 8 every 21 d

9. SECOND-LINE CHEMOTHERAPY,
METASTATIC OR RECURRENT DISEASE
STAGE IV OR RECURRENT DISEASE
Second-line chemotherapy is given for advanced or recurrent disease after disease progression
following first-line therapy. Second-line regimens are as follows:
Nivolumab 3 mg/kg IV every 2 weeks until disease progression or unacceptable toxicity or
Pembrolizumab 200 mg IV every 3 weeks until disease progression or unacceptable toxicity (for up to
24 mo) in tumors that are PD-L1 positive; patients with EGFR or ALK genomic tumor aberrations
should have disease progression on FDA-approved therapy for these aberrations prior to receiving
pembrolizumab or
Docetaxel 75 mg/m 2 IV on day 1 every 21 d (goal, four to six cycles) +/- ramucirumab 10 mg/kg
IV or
Pemetrexed 500 mg/m 2 IV on day 1 (non-squamous histology) every 21 d (goal, four to six cycles;
include folate and vitamin B12 supplements along with dexamethasone premedication for
pemetrexed) or
Erlotinib 150 mg PO daily for patients with EGFR mutation or gene amplification; given until disease
progression
Afatinib 40 mg PO daily for patients with metastatic squamous NSCLC that has progressed after
platinum-based chemotherapy

10. THIRD-LINE CHEMOTHERAPY,
METASTATIC OR RECURRENT DISEASE
STAGE IV OR RECURRENT DISEASE
Third-line chemotherapy is given for advanced or recurrent non–small cell lung cancer (NSCLC)
after disease progression following first-line and second-line therapy. Options include erlotinib,
ramucirumab, and nivolumab.
Erlotinib is indicated for patients with EGFR mutation or gene amplification. It is given in a
dosage of 150 mg PO daily until disease progression.
Ramucirumab is indicated for metastatic NSCLC with disease progression on or after platinum-
based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease
progression on FDA-approved therapy for these aberrations prior to receiving ramucirumab. The
regimen is as follows:
Ramucirumab 10 mg/kg IV infused over ~1 h prior to docetaxel (75 mg/m 2) IV infusion on day
1 of a 21-d cycle; continue until disease progression or unacceptable toxicity
Nivolumab is indicated for metastatic squamous and nonsquamous (including adenomas) NSCLC
with progression on or after platinum-based chemotherapy.
The regimen is as follows:

11. SINGLE-AGENT THERAPY, METASTATIC
OR RECURRENT DISEASE
STAGE IV OR RECURRENT DISEASE
Single-agent therapy is a reasonable first-line option in patients with good
performance status (ECOG score ≤2) disease or in the elderly; the goal is to complete
four to six cycles.
Single-agent regimens include the following:
Paclitaxel 200 mg/m 2 IV every 21 d or
Docetaxel 35 mg/m 2 IV weekly for 3 wk every 4wk or
Gemcitabine 1000 mg/m 2 IV on days 1, 8, and 15 every 4 wk or
Pemetrexed 500 mg/m 2 IV every 21d (non-squamous histology)

12. Pembrolizumab may be used first-line with NSCLC with high PD-L1 expression (TPS ≥50%) with no EGFR or ALK
genomic tumor aberrations or after platinum-containing chemotherapy for tumors that express PD-L1 (TPS
≥1%); patients with EGFR or ALK aberrations should have disease progression on FDA-approved therapy for
these aberrations before receiving pembrolizumab; dose as follows: [61, 69]
Pembrolizumab 200 mg IV every 3 weeks; continue until disease progression or unacceptable toxicity (for up to
24 mo)
EGFR T790M mutation positive NSCLC detected by an FDA approved test, in patients who have progressed on or
after EGFR TKI therapy
Osimertinib 80 mg PO once daily until disease progression or unacceptable toxicity
ROS-1 mutation positive NSCLC
Crizotinib 250 mg PO q12h until disease progression or unacceptable toxicity
ALK-positive metastatic NSCLC
Ceritinib 750mg PO qDay until disease progression or unacceptable toxicity
Alectinib 600mg PO q12h until disease progression or unacceptable toxicity
ALK-positive metastatic NSCLC in patient who have progressed on or are intolerant to crizotinib
Brigatinib 90 mg PO q Day for the first 7 days; if 90 mg/day is tolerated, increase the dose to 180 mg PO until
disease progression or unacceptable toxicity
Disease progression during or following platinum-containing chemotherapy; patients with EGFR or ALK genomic
tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to
receiving atezolizumab
Atezolizumab 1200 mg IV q3wk until disease progression or unacceptable toxicity

13. MAINTENANCE CHEMOTHERAPY,
METASTATIC OR RECURRENT DISEASE
STAGE IV DISEASE
Maintenance chemotherapy may be considered for patients with advanced (stage IV) disease who
have a disease response or stable disease after completing first-line chemotherapy
Switch Maintenance Chemotherapy
Switch maintenance chemotherapy involves giving chemotherapy with agents different from
those used in first-line therapy. This chemotherapy is given after completing first-line
chemotherapy until disease progression or unacceptable toxicities occur. Switch maintenance
therapy is associated with improvements in progression-free survival for all three agents listed
below and improvements in overall survival for pemetrexed and erlotinib.
Switch maintenance chemotherapy regimens are as follows:
Docetaxel 75 mg/m 2 IV every 21 d or
Pemetrexed 500 mg/m 2 IV every 21 d (non-squamous histology) or
Erlotinib 150 mg PO daily (1 h before or 2 h after meals)
Ref: https://emedicine.medscape.com/article/2007153-overview#showall

14. SOME BEACON’S BRANDS FOR CHEMO:
PLATINEX
CISPLATIN

15. TOPOXIN
ETOPOSIDE

16. GEMOXEN
GEMCITABINE

17. DOCEXAN
DOCETAXEL

18. PEMETREX
PEMETREXED

19. CARBOPLAT
CARBOPLATIN

20. XELPAC
PACLITAXEL

21. ERLONIX
ERLOTINIB

22. AFANIX
AFATINIB

23. GEFINIX
GEFITINIB

24. CRIZONIX
CRIZOTINIB

25. TAGRIX
OSIMERTINIB

26. THANK
YOU
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