Paclinab

Paclinab ® is a microtubule inhibitor indicated for the treatment of paitients with Metastatic breast cancer, Locally advanced or metastatic non-small cell lung cancer, Metastatic adenocarcinoma of pancreas.

 is recommended by guidelines such as NCCN and ESMO as first line regimens in metastatic pancreatic cancer in combination with gemcitabine and and in non-small cell lung cancer in combination with carboplatin.

Name of the medicinal product:

Paclinab® (Paclitaxel albumin-bound particles) 100 mg Powder for Suspension

List of excipients:

Human serum albumin solution (containing sodium, sodium caprylate and N-acetyl DL tryptophanate).

Pharmaceutical form:

Sterile Lyophilized Powder for Suspension. Each vial contains 100 mg of paclitaxel formulated as albumin bound nanoparticles. After reconstitution, each mL of suspension contains 5 mg of paclitaxel formulated as albumin bound nanoparticles.

Side Effect Management

Dose Adjustment For Hematologic And Neurologic Adverse Reactions In NSCLC

Adverse Drug Reaction Occurrence Weekly
PACLINAB Dose
(mg/m2)
Every 3-Week
Carboplatin Dose
(AUC mg•min/mL)
Neutropenic Fever (ANC less than 500/mm3 with fever >38°C)
OR
Delay of next cycle by more than 7 days for ANC less than 1500/mm3
OR
ANC less than 500/mm3 for more than 7 days
First 75 4.5
Second 50 3
Third Discontinue Treatment
Platelet count less than 50,000/mm3 First 75 4.5
Second Discontinue Treatment
Severe sensory Neuropathy – Grade 3 or 4 First 75 4.5
Second 50 3
Third Discontinue Treatment

Dose Level Reductions for Patients with Adenocarcinoma of the Pancreas

 

Dose Level PACLINAB (mg/m2) Gemcitabine (mg/m2)
Full dose 125 1000
1st dose reduction 100 800
2nd dose reduction 75 600
If additional dose reduction required Discontinue Discontinue

Dose Recommendation and Modifications for Neutropenia and/or Thrombocytopenia at the Start of a Cycle or within a Cycle for Patients with Adenocarcinoma of the Pancreas

Cycle Day ANC (cells/mm3 Platelet count (cells/mm3) PACLINAB / Gemcitabine
Day 1 < 1500 OR < 100,000 Delay doses until recovery
Day 8 500 to < 1000 OR 50,000 to < 75,000 Reduce 1 dose level
< 500 OR < 50,000 Withhold doses
Day 15: If Day 8 doses were reduced or given without modification:
500 to < 1000 OR 50,000 to < 75,000 Reduce 1 dose level from Day 8
< 500 OR < 50,000 Withhold doses
Day 15: If Day 8 doses were withheld:
≥ 1000 OR ≥ 75,000 Reduce 1 dose level from Day 1
500 to < 1000 OR 50,000 to < 75,000 Reduce 2 dose levels from Day 1
< 500 OR < 50,000 Withhold doses

ANC = Absolute Neutrophil Count
Recommended dose modifications for other adverse drug reactions in patients with adenocarcinoma of the pancreas are provided in
Table 5.
Dose Modifications for Other Adverse Drug Reactions in Patients with Adenocarcinoma of the Pancreas

Adverse Drug Reaction PACLINAB Gemcitabine
Febrile Neutropenia:
Grade 3 or 4
Withhold until fever resolves and ANC ≥ 1500; resume at next lower dose level
Peripheral Neuropathy:
Grade 3 or 4
Withhold until improves to ≤ Grade 1;
resume at next lower dose level
No dose reduction
Cutaneous Toxicity:
Grade 2 or 3
Reduce to next lower dose level; discontinue treatment if toxicity persists
Gastrointestinal Toxicity:
Grade 3 mucositis or diarrhea
Withhold until improves to ≤ Grade 1;
resume at next lower dose level

 

SGOT (AST)
Levels
Bilirubin
Levels
MBC NSCLC c Pancreatic c
Adenocarcinoma
Mild < 10 x ULN AND > ULN to ≤ 1. 5 x ULN 260 mg/m2 100 mg/m2 125 mg/m2
Moderate < 10 x ULN AND > 1.5 to ≤ 3 x ULN 200 mg/m2 b 80 mg/m2 b not recommended
Severe < 10 x ULN AND > 3 to ≤ 5 x ULN 200 mg/m2 b 80 mg/m2 b not recommended
Severe > 10 x ULN OR    > 5 x ULN not recommended not recommended not recommended

MBC = Metastatic Breast Cancer; NSCLC = Non-Small Cell Lung Cancer.

a Dosage recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance.

b A dose increase to 260 mg/m2 for patients with metastatic breast cancer or 100 mg/m2 for patients with non-small cell lung cancer in subsequent courses should be considered if the patient tolerates the reduced dose for two cycles.

c Patients with bilirubin levels above the upper limit of normal were excluded from clinical trials for pancreatic or lung cancer.

Metastatic Breast Cancer Dose Modification

Patients who experience severe neutropenia (neutrophils less than 500 cells/mm3 for a week or longer) or severe sensory neuropathy during Paclinab therapy should have dosage reduced to 220 mg/m2 for subsequent courses of Paclinab. For recurrence of severe neutropenia or severe sensory neuropathy, additional dose reduction should be made to 180 mg/m2. For Grade 3 sensory neuropathy hold treatment until resolution to Grade 1 or 2, followed by a dose reduction for all subsequent courses of Paclinab.

Administration

Final Paclinab® concentration

( mg/ml)

Diluent( 0.9% sodium chloride) Paclinab® (mg/vial)

 

5 mg/ml 20 ml 100 mg
260 or 125 or 100 (mg/m2) x patient BSA (m2)
5 (mg/ml)
= Total Paclinab ® volume (ml) to be administered

Dosing

Posology
Pancreatic adenocarcinoma The recommended dose of Paclinab® in combination with gemcitabine is 125 mg/m2 administered intravenously over 30 minutes on Days 1, 8 and 15 of each 28-day cycle. The concurrent recommended dose of gemcitabine is 1000 mg/m2 administered intravenously over 30 minutes immediately after the completion of Paclinab® administration on Days 1, 8 and 15 of each 28-day cycle.
Non-small cell lung cancer The recommended dose of Paclinab® is 100 mg/m2 administered as an intravenous infusion over 30 minutes on Days 1, 8 and 15 of each 21-day cycle. The recommended dose of carboplatin is AUC = 6 mg*min/mL on Day 1 only of each 21-day cycle, beginning immediately after the end of Paclinab® administration.
Metastatic breast cancer The recommended dose of Paclinab® is 260 mg/m2 administered intravenously over 30 minutes every 3 weeks.

Another recommended dose of Paclinab® is 125 mg/m2 administered intravenously over 30 minutes on Days 1, 8 and 15 of each 28-day cycle.

NCCN Guidelines Version 2.2017 for breast cancer
CHEMOTHERAPY REGIMENS FOR RECURRENT OR METASTATIC BREAST CANCER
Single agents Preferred single agents:
  • Anthracyclines
  • Doxorubicin
  • Pegylated liposomal doxorubicin
  • Taxanes
  • Paclitaxel
  • Anti-metabolites
  • Capecitabine
  • Gemcitabine Other microtubule inhibitors
  • Vinorelbine
  • Eribulin
Other single agents:
  • Cyclophosphamide
  • Carboplatin
  • Docetaxel
  • Albumin-bound paclitaxel
  • Cisplatin
  • Epirubicin
  • Ixabepilone
Chemotherapy combinations:
  • CAF/FAC (cyclophosphamide/doxorubicin/fluorouracil)
  • FEC (fluorouracil/epirubicin/cyclophosphamide)
  • AC (doxorubicin/cyclophosphamide)
  • EC (epirubicin/cyclophosphamide)
  • CMF (cyclophosphamide/methotrexate/fluorouracil)
  • Docetaxel/capecitabine
  • GT (gemcitabine/paclitaxel)
  • Gemcitabine/carboplatin
  • Paclitaxel/bevacizumab
HER2-positive regiments Preferred first-line agents for HER2-positive disease:
  • Pertuzumab + trastuzumab + docetaxel (category 1)
  • Pertuzumab + trastuzumab + paclitaxel
Other agents for HER2-positive disease
  • Ado-trastuzumab emtansine (T-DM1)
  • Trastuzumab + paclitaxel ± carboplatin
  • Trastuzumab + docetaxel
  • Trastuzumab + vinorelbine
  • Trastuzumab + capecitabine

Nab-paclitaxel may be substituted for paclitaxel or docetaxel due to medical necessity (ie, hypersensitivity reaction). If substituted for weekly paclitaxel or docetaxel, then the weekly dose of nabpaclitaxel should not exceed 125 mg/m2

NCCN Guidelines Version 2.2017 for Pancreatic Adenocarcinoma
PRINCIPLES OF CHEMOTHERAPY
Neoadjuvant Therapy (Resectable/Borderline Resectable Disease) FOLFIRINOX ± subsequent chemoradiation

 

Gemcitabine + albumin-bound paclitaxel ± subsequent chemoradiation

 

Gemcitabine + cisplatin (≥2–6 cycles) followed by chemoradiation (reserved for patients with BRCA1/BRCA2 or other DNA repair mutations)

Locally Advanced/Unresectable Disease (First-Line Therapy) patients with good performance status FOLFIRINOX

Gemcitabine + albumin-bound paclitaxela,

Gemcitabine + erlotinibc,

Gemcitabine + capecitabine

Gemcitabine + cisplatin

Gemcitabine

Capecitabine

CI 5-FU

Fixed-dose-rate gemcitabine, docetaxel, capecitabine

Fluoropyrimidine + oxaliplatin

patients with poor performance status GemcitabineCapecitabine CI 5-FU
Metastatic Disease First-Line Therapy patients with good performance status FOLFIRINOX  (preferred)

Gemcitabine + albumin-bound paclitaxel (preferred)

Gemcitabine + erlotinibc

Gemcitabine

Gemcitabine + capecitabine

Gemcitabine + cisplatin10

Fixed-dose-rate gemcitabine, docetaxel, capecitabine

Fluoropyrimidine + oxaliplatin

patients with poor performance status  Gemcitabin
Capecitabine
CI 5-FU
Second-line Therapy • If previously treated with gemcitabine-based therapy 5-FU + leucovorin + liposomal irinotecanf

FOLFIRINOXf

Oxaliplatin/5-FU/leucovorin

FOLFOX Capecitabine/oxaliplatin

Capecitabine

CI 5-FU

Chemoradiation

• If previously treated with fluoropyrimidine-based therapy Gemcitabine + albumin-bound paclitaxelf Gemcitabine

Gemcitabine + cisplatin Gemcitabine + erlotinib

5-FU + leucovorin + liposomal irinotecan

Chemoradiation*

Recurrent Disease If resected patients with good performance status relapse after receiving adjuvant therapy, FOLFIRINOX or gemcitabine + albumin-bound paclitaxel are options depending on the length of time since completion of adjuvant therapy
NCCN Guidelines Version 2.2017  for  Non-Small Cell Lung Cancer
SYSTEMIC THERAPY FOR ADVANCED OR METASTATIC DISEASE
First-line Systemic Therapy Options Adenocarcinoma, Large Cell, NSCLC Adenocarcinoma, Large Cell, NSCLC NOS (PS 0-1) Bevacizumab/carboplatin/paclitaxel
Bevacizumab/carboplatin/pemetrexed
Bevacizumab/cisplatin/pemetrexed
Carboplatin/albumin-bound paclitaxel
Carboplatin/docetaxel
Carboplatin/etoposide
Carboplatin/gemcitabine
Carboplatin/paclitaxel
Carboplatin/pemetrexed
Cisplatin/docetaxel
Cisplatin/etoposide
Cisplatin/gemcitabine
Cisplatin/paclitaxel
Cisplatin/pemetrexed
Gemcitabine/docetaxel
Gemcitabine/vinorelbine
Adenocarcinoma, Large Cell, NSCLC NOS (PS 2) Albumin-bound paclitaxel
Carboplatin/albumin-bound paclitaxel
Carboplatin/docetaxel
Carboplatin/etoposide
Carboplatin/gemcitabine
Carboplatin/paclitaxel
Carboplatin/pemetrexed
Docetaxel
Gemcitabine
Gemcitabine/docetaxel
Gemcitabine/vinorelbine
Paclitaxel
Pemetrexed
Squamous Cell Carcinoma (PS 0-1) Carboplatin/albumin-bound paclitaxel
Carboplatin/docetaxel
Carboplatin/gemcitabine
Carboplatin/paclitaxel
Cisplatin/docetaxel
Cisplatin/etoposide
Cisplatin/gemcitabine
Cisplatin/paclitaxel
Gemcitabine/docetaxel
Gemcitabine/vinorelbine
First-line Systemic Therapy Options Squamous Cell Carcinoma Squamous Cell Carcinoma (PS 2) Albumin-bound paclitaxel
Carboplatin/albumin-bound paclitaxel
Carboplatin/docetaxel
Carboplatin/etoposide
Carboplatin/gemcitabine
Carboplatin/paclitaxel
Docetaxel
Gemcitabine
Gemcitabine/docetaxel
Gemcitabine/vinorelbine
Paclitaxel

Albumin-bound paclitaxel may be substituted for either paclitaxel or docetaxel in patients who have experienced hypersensitivity reactions after receiving paclitaxel or docetaxel despite premedication, or for patients where the standard premedications (ie, dexamethasone, H2 blockers, H1 blockers) are contraindicated