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: |
|
| Other single agents: |
|
|
| Chemotherapy combinations: |
|
|
| HER2-positive regiments | Preferred first-line agents for HER2-positive disease: |
|
| Other agents for HER2-positive disease |
|
|
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
Articles
Efcacy and safety of nanoparticlealbumin-bound paclitaxel compared with solvent based taxanes for metastatic breast cancer: A meta-analysis
Nab-paclitaxel: first-line treatment of metastatic breast cancer
Please read below a meta-analysis on 5 RCTs containing 1554 eligible patients to see whether nanoparticle-albumin-bound paclitaxel (nab-paclitaxel) had a certain benefit over conventional solvent-based taxanes (sb-taxanes) in terms of efficacy and toxicities in the first-line treatment of metastatic breast cancer.
Subgroup analysis within the single taxane subgroup, showed that nab-paclitaxel was superior to sb-paclitaxel in terms of overall response rate (ORR), disease control rate (DCR) and progression-free survival (PFS). Nab-paclitaxel was also superior to docetaxel on overall survival (OS) and DCR.
Conclusively these data indicate that nab-paclitaxel is an effective anti-tumor drug in the first-line treatment of metastatic breast cancer.
Nano Daru is manufacturing nab-paclitaxel under the brand name Paclinab®