Axtle
(Pemetrexed)Axtle Prescribing Information
Dosage and Administration (
- AXTLE is a hazardous drug. Follow applicable special handling and disposal procedures.1
- Calculate the dose of AXTLE and determine the number of vials needed.
- Reconstitute AXTLE to achieve a concentration of 25 mg/mL as follows:
▪ Reconstitute each 500-mg vial with 20 mL of 5% Dextrose Injection, USP (preservative-free) or 0.9% Sodium Chloride Injection, USP (preservative-free)
▪ Do not use calcium-containing solutions for reconstitution.
- Gently swirl each vial until the powder is completely dissolved. The resulting solution is clear and ranges in color from colorless to yellow or green-yellow. FURTHER DILUTION IS REQUIRED prior to administration.
- Store reconstituted, preservative-free product under refrigerated conditions [2-8°C (36-46°F)] for no longer than 24 hours from the time of reconstitution. Discard vial after 24 hours.
- Inspect reconstituted product visually for particulate matter and discoloration prior to further dilution. If particulate matter is observed, discard vial.
- Withdraw the calculated dose of AXTLE from the vial(s) and discard vial with any unused portion.
- Store diluted, reconstituted product under refrigerated conditions [2-8°C (36-46°F)] for no more than 24 hours from the time of reconstitution. Discard after 24 hours.
AXTLE is a folate analog metabolic inhibitor indicated:
- in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous NSCLC. ()1.1 Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
AXTLE is indicated for:
- in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous NSCLC.
- as a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
- as a single agent for the treatment of patients with recurrent, metastatic non-squamous, NSCLC after prior chemotherapy.
Limitations of Use:AXTLE is not indicated for the treatment of patients with squamous cell, non-small cell lung cancer[see Clinical Studies (14.1)]. - as a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. ()1.1 Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
AXTLE is indicated for:
- in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous NSCLC.
- as a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
- as a single agent for the treatment of patients with recurrent, metastatic non-squamous, NSCLC after prior chemotherapy.
Limitations of Use:AXTLE is not indicated for the treatment of patients with squamous cell, non-small cell lung cancer[see Clinical Studies (14.1)]. - as a single agent for the treatment of patients with recurrent, metastatic non-squamous, NSCLC after prior chemotherapy. ()1.1 Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
AXTLE is indicated for:
- in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous NSCLC.
- as a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
- as a single agent for the treatment of patients with recurrent, metastatic non-squamous, NSCLC after prior chemotherapy.
Limitations of Use:AXTLE is not indicated for the treatment of patients with squamous cell, non-small cell lung cancer[see Clinical Studies (14.1)].
AXTLE is indicated for:
- in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous NSCLC.
- as a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
- as a single agent for the treatment of patients with recurrent, metastatic non-squamous, NSCLC after prior chemotherapy.
- initial treatment, in combination with cisplatin, of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. ()1.2 Mesothelioma
AXTLE is indicated, in combination with cisplatin, for the initial treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery.
- The recommended dose of AXTLE, administered as a single agent or with cisplatin, in patients with creatinine clearance of 45 mL/minute or greater is 500 mg/m2as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle. (,2.1 Recommended Dosage for Non-Squamous NSCLC
- The recommended dose of AXTLE when administered with cisplatin for initial treatment of locally advanced or metastatic non-squamous NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2as an intravenous infusion over 10 minutes administered prior to cisplatin on Day 1 of each 21-day cycle for up to six cycles in the absence of disease progression or unacceptable toxicity.
- The recommended dose of AXTLE for maintenance treatment of non-squamous NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity after four cycles of platinum-based first-line chemotherapy.
- The recommended dose of AXTLE for treatment of recurrent non-squamous NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
)2.2 Recommended Dosage for Mesothelioma- The recommended dose of AXTLE, when administered with cisplatin, in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
- Initiate folic acid 400 mcg to 1000 mcg orally, once daily, beginning 7 days prior to the first dose of AXTLE and continue until 21 days after the last dose of AXTLE. ()2.4 Premedication and Concomitant Medications to Mitigate ToxicityVitamin Supplementation
- Initiate folic acid 400 mcg to 1000 mcg orally once daily, beginning 7 days before the first dose of AXTLE and continuing until 21 days after the last dose of AXTLE[see Warnings and Precautions (5.1)].
- Administer vitamin B12,1 mg intramuscularly, 1 week prior to the first dose of AXTLE and every 3 cycles thereafter. Subsequent vitamin B12injections may be given the same day as treatment with AXTLE[see Warnings and Precautions (5.1)].Do not substitute oral vitamin B12for intramuscular vitamin B12.
Corticosteroids- Administer dexamethasone 4 mg orally twice daily for three consecutive days, beginning the day before each AXTLE administration.
- Initiate folic acid 400 mcg to 1000 mcg orally once daily, beginning 7 days before the first dose of AXTLE and continuing until 21 days after the last dose of AXTLE
- Administer vitamin B12, 1 mg intramuscularly, 1 week prior to the first dose of AXTLE and every 3 cycles. ()2.4 Premedication and Concomitant Medications to Mitigate ToxicityVitamin Supplementation
- Initiate folic acid 400 mcg to 1000 mcg orally once daily, beginning 7 days before the first dose of AXTLE and continuing until 21 days after the last dose of AXTLE[see Warnings and Precautions (5.1)].
- Administer vitamin B12,1 mg intramuscularly, 1 week prior to the first dose of AXTLE and every 3 cycles thereafter. Subsequent vitamin B12injections may be given the same day as treatment with AXTLE[see Warnings and Precautions (5.1)].Do not substitute oral vitamin B12for intramuscular vitamin B12.
Corticosteroids- Administer dexamethasone 4 mg orally twice daily for three consecutive days, beginning the day before each AXTLE administration.
- Initiate folic acid 400 mcg to 1000 mcg orally once daily, beginning 7 days before the first dose of AXTLE and continuing until 21 days after the last dose of AXTLE
- Administer dexamethasone 4 mg orally, twice daily the day before, the day of, and the day after AXTLE administration. ()2.4 Premedication and Concomitant Medications to Mitigate ToxicityVitamin Supplementation
- Initiate folic acid 400 mcg to 1000 mcg orally once daily, beginning 7 days before the first dose of AXTLE and continuing until 21 days after the last dose of AXTLE[see Warnings and Precautions (5.1)].
- Administer vitamin B12,1 mg intramuscularly, 1 week prior to the first dose of AXTLE and every 3 cycles thereafter. Subsequent vitamin B12injections may be given the same day as treatment with AXTLE[see Warnings and Precautions (5.1)].Do not substitute oral vitamin B12for intramuscular vitamin B12.
Corticosteroids- Administer dexamethasone 4 mg orally twice daily for three consecutive days, beginning the day before each AXTLE administration.
- Initiate folic acid 400 mcg to 1000 mcg orally once daily, beginning 7 days before the first dose of AXTLE and continuing until 21 days after the last dose of AXTLE
For injection: 100 mg or 500 mg pemetrexed equivalent to 118.3 mg or 591.5 mg pemetrexed dipotassium as a sterile preservative free white to light-yellow or green-yellow lyophilized powder in single-dose vials for reconstitution.
Lactation: Advise not to breastfeed. (
There is no information regarding the presence of pemetrexed or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from pemetrexed, advise women not to breastfeed during treatment with AXTLE and for one week after last dose.
AXTLE is contraindicated in patients with a history of severe hypersensitivity reaction to pemetrexed
Because clinical trials are conducted under widely varying conditions, adverse reactions rates cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice.
In clinical trials, the most common adverse reactions (incidence ≥20%) of pemetrexed, when administered as a single agent, are fatigue, nausea, and anorexia. The most common adverse reactions (incidence ≥20%) of pemetrexed, when administered in combination with cisplatin are vomiting, neutropenia, anemia, stomatitis/pharyngitis, thrombocytopenia, and constipation.
The safety of pemetrexed was evaluated in Study JMDB, a randomized (1:1), open-label, multicenter trial conducted in chemotherapy-naive patients with locally advanced or metastatic NSCLC. Patients received either pemetrexed 500 mg/m2intravenously and cisplatin 75 mg/m2intravenously on Day 1 of each 21-day cycle (n=839) or gemcitabine 1250 mg/m2intravenously on Days 1 and 8 and cisplatin 75 mg/m2intravenously on Day 1 of each 21-day cycle (n=830). All patients were fully supplemented with folic acid and vitamin B12.
Study JMDB excluded patients with an Eastern Cooperative Oncology Group Performance Status (ECOG PS of 2 or greater), uncontrolled third-space fluid retention, inadequate bone marrow reserve and organ function, or a calculated creatinine clearance less than 45 mL/min. Patients unable to stop using aspirin or other non-steroidal anti-inflammatory drugs or unable to take folic acid, vitamin B12or corticosteroids were also excluded from the study.
The data described below reflect exposure to pemetrexed plus cisplatin in 839 patients in Study JMDB. Median age was 61 years (range 26-83 years); 70% of patients were men; 78% were White,16% were Asian, 2.9% were Hispanic or Latino, 2.1% were Black or African American, and <1% were other ethnicities; 36% had an ECOG PS 0. Patients received a median of 5 cycles of pemetrexed.
Table 2 provides the frequency and severity of adverse reactions that occurred in ≥5% of 839 patients receiving pemetrexed in combination with cisplatin in Study JMDB. Study JMDB was not designed to demonstrate a statistically significant reduction in adverse reaction rates for pemetrexed, as compared to the control arm, for any specified adverse reaction listed in Table 2.
aNCI CTCAE version 2.0. | ||||
Adverse Reactiona | Pemetrexed/Cisplatin (N=839) | Gemcitabine/Cisplatin (N=830) | ||
All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | |
All adverse reactions | 90 | 37 | 91 | 53 |
Laboratory | ||||
Hematologic | ||||
| Anemia | 33 | 6 | 46 | 10 |
| Neutropenia | 29 | 15 | 38 | 27 |
| Thrombocytopenia | 10 | 4 | 27 | 13 |
Renal | ||||
| Elevated creatinine | 10 | 1 | 7 | 1 |
Clinical | ||||
Constitutional symptoms | ||||
| Fatigue | 43 | 7 | 45 | 5 |
Gastrointestinal | ||||
| Nausea | 56 | 7 | 53 | 4 |
| Vomiting | 40 | 6 | 36 | 6 |
| Anorexia | 27 | 2 | 24 | 1 |
| Constipation | 21 | 1 | 20 | 0 |
| Stomatitis/pharyngitis | 14 | 1 | 12 | 0 |
| Diarrhea | 12 | 1 | 13 | 2 |
| Dyspepsia/heartburn | 5 | 0 | 6 | 0 |
Neurology | ||||
| Sensory neuropathy | 9 | 0 | 12 | 1 |
| Taste disturbance | 8 | 0 | 9 | 0 |
Dermatology/Skin | ||||
| Alopecia | 12 | 0 | 21 | 1 |
| Rash/Desquamation | 7 | 0 | 8 | 1 |
The following additional adverse reactions of pemetrexed were observed.
In Study JMEN, the safety of pemetrexed was evaluated in a randomized (2:1), placebo-controlled, multicenter trial conducted in patients with non-progressive locally advanced or metastatic NSCLC following four cycles of a first-line, platinum-based chemotherapy regimen. Patients received either pemetrexed 500 mg/m2or matching placebo intravenously every 21 days until disease progression or unacceptable toxicity. Patients in both study arms were fully supplemented with folic acid and vitamin B12.
Study JMEN excluded patients with an ECOG PS of 2 or greater, uncontrolled third-space fluid retention, inadequate bone marrow reserve and organ function, or a calculated creatinine clearance less than 45 mL/min. Patients unable to stop using aspirin or other non-steroidal anti-inflammatory drugs or unable to take folic acid, vitamin B12or corticosteroids were also excluded from the study.
The data described below reflect exposure to pemetrexed in 438 patients in Study JMEN. Median age was 61 years (range 26-83 years), 73% of patients were men; 65% were White, 31% were Asian, 2.9% were Hispanic or Latino, and <2% were other ethnicities; 39% had an ECOG PS 0. Patients received a median of 5 cycles of pemetrexed and a relative dose intensity of pemetrexed of 96%. Approximately half the patients (48%) completed at least six, 21-day cycles and 23% completed ten or more 21-day cycles of pemetrexed.
Table 3 provides the frequency and severity of adverse reactions reported in ≥5% of the 438 pemetrexed-treated patients in Study JMEN.
aNCI CTCAE version 3.0 | ||||
Adverse Reactiona | Pemetrexed (N=438) | Placebo (N=218) | ||
All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | |
All adverse reactions | 66 | 16 | 37 | 4 |
Laboratory | ||||
Hematologic | ||||
| Anemia | 15 | 3 | 6 | 1 |
| Neutropenia | 6 | 3 | 0 | 0 |
Hepatic | ||||
| Increased ALT | 10 | 0 | 4 | 0 |
| Increased AST | 8 | 0 | 4 | 0 |
Clinical | ||||
Constitutional symptoms | ||||
| Fatigue | 25 | 5 | 11 | 1 |
Gastrointestinal | ||||
| Nausea | 19 | 1 | 6 | 1 |
| Anorexia | 19 | 2 | 5 | 0 |
| Vomiting | 9 | 0 | 1 | 0 |
| Mucositis/stomatitis | 7 | 1 | 2 | 0 |
| Diarrhea | 5 | 1 | 3 | 0 |
Infection | 5 | 2 | 2 | 0 |
Neurology | ||||
| Sensory neuropathy | 9 | 1 | 4 | 0 |
Dermatology/Skin | ||||
| Rash/desquamation | 10 | 0 | 3 | 0 |
The requirement for transfusions (9.5% versus 3.2%), primarily red blood cell transfusions, and for erythropoiesis stimulating agents (5.9% versus 1.8%) were higher in the pemetrexed arm compared to the placebo arm.
The following additional adverse reactions were observed in patients who received pemetrexed.
The safety of pemetrexed was evaluated in PARAMOUNT, a randomized (2:1), placebo-controlled study conducted in patients with non-squamous NSCLC with non-progressive (stable or responding disease) locally advanced or metastatic NSCLC following four cycles of pemetrexed in combination with cisplatin as first-line therapy for NSCLC. Patients were randomized to receive pemetrexed 500 mg/m2or matching placebo intravenously on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity. Patients in both study arms received folic acid and vitamin B12supplementation.
PARAMOUNT excluded patients with an ECOG PS of 2 or greater, uncontrolled third-space fluid retention, inadequate bone marrow reserve and organ function, or a calculated creatinine clearance less than 45 mL/min. Patients unable to stop using aspirin or other non-steroidal anti-inflammatory drugs or unable to take folic acid, vitamin B12or corticosteroids were also excluded from the study.
The data described below reflect exposure to pemetrexed in 333 patients in PARAMOUNT. Median age was 61 years (range 32 to 83 years); 58% of patients were men; 94% were White, 4.8% were Asian, and <1% were Black or African American; 36% had an ECOG PS 0. The median number of maintenance cycles was 4 for pemetrexed and placebo arms. Dose reductions for adverse reactions occurred in 3.3% of patients in the pemetrexed arm and 0.6% in the placebo arm. Dose delays for adverse reactions occurred in 22% of patients in the pemetrexed arm and 16% in the placebo arm.
Table 4 provides the frequency and severity of adverse reactions reported in ≥5% of the 333 pemetrexed-treated patients in PARAMOUNT.
aNCI CTCAE version 3.0 | ||||
Adverse Reactiona | Pemetrexed (N=333) | Placebo (N=167) | ||
All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grades 3-4 (%) | |
All adverse reactions | 53 | 17 | 34 | 4.8 |
Laboratory | ||||
Hematologic | ||||
| Anemia | 15 | 4.8 | 4.8 | 0.6 |
| Neutropenia | 9 | 3.9 | 0.6 | 0 |
Clinical | ||||
Constitutional symptoms | ||||
| Fatigue | 18 | 4.5 | 11 | 0.6 |
Gastrointestinal | ||||
| Nausea | 12 | 0.3 | 2.4 | 0 |
| Vomiting | 6 | 0 | 1.8 | 0 |
| Mucositis/stomatitis | 5 | 0.3 | 2.4 | 0 |
General disorders | ||||
| Edema | 5 | 0 | 3.6 | 0 |
The requirement for red blood cell (13% versus 4.8%) and platelet (1.5% versus 0.6%) transfusions, erythropoiesis stimulating agents (12% versus 7%), and granulocyte colony stimulating factors (6% versus 0%) were higher in the pemetrexed arm compared to the placebo arm.
The following additional Grade 3 or 4 adverse reactions were observed more frequently in the pemetrexed arm.
The safety of pemetrexed was evaluated in Study JMEI, a randomized (1:1), open-label, active-controlled trial conducted in patients who had progressed following platinum-based chemotherapy. Patients received pemetrexed 500 mg/m2intravenously or docetaxel 75 mg/m2intravenously on Day 1 of each 21-day cycle. All patients on the pemetrexed arm received folic acid and vitamin B12supplementation.
Study JMEI excluded patients with an ECOG PS of 3 or greater, uncontrolled third-space fluid retention, inadequate bone marrow reserve and organ function, or a calculated creatinine clearance less than 45 mL/min. Patients unable to discontinue aspirin or other non-steroidal anti-inflammatory drugs or unable to take folic acid, vitamin B12or corticosteroids were also excluded from the study.
The data described below reflect exposure to pemetrexed in 265 patients in Study JMEI. Median age was 58 years (range 22 to 87 years); 73% of patients were men; 70% were White, 24% were Asian, 2.6% were Black or African American, 1.8% were Hispanic or Latino, and <2% were other ethnicities; 19% had an ECOG PS 0.
Table 5 provides the frequency and severity of adverse reactions reported in ≥5% of the 265 pemetrexed-treated patients in Study JMEI. Study JMEI is not designed to demonstrate a statistically significant reduction in adverse reaction rates for pemetrexed, as compared to the control arm, for any specified adverse reaction listed in the Table 5 below.
aNCI CTCAE version 2.0. | ||||
Adverse Reactiona | Pemetrexed (N=265) | Docetaxel (N=276) | ||
All Grades (%) | Grades 3-4 (%) | All Grades (%) | Grades 3-4 (%) | |
Laboratory | ||||
Hematologic | ||||
| Anemia | 19 | 4 | 22 | 4 |
| Neutropenia | 11 | 5 | 45 | 40 |
| Thrombocytopenia | 8 | 2 | 1 | 0 |
Hepatic | ||||
| Increased ALT | 8 | 2 | 1 | 0 |
| Increased AST | 7 | 1 | 1 | 0 |
Clinical | ||||
Gastrointestinal | ||||
| Nausea | 31 | 3 | 17 | 2 |
| Anorexia | 22 | 2 | 24 | 3 |
| Vomiting | 16 | 2 | 12 | 1 |
| Stomatitis/pharyngitis | 15 | 1 | 17 | 1 |
| Diarrhea | 13 | 0 | 24 | 3 |
| Constipation | 6 | 0 | 4 | 0 |
Constitutional symptoms | ||||
| Fatigue | 34 | 5 | 36 | 5 |
| Fever | 8 | 0 | 8 | 0 |
Dermatology/Skin | ||||
| Rash/desquamation | 14 | 0 | 6 | 0 |
| Pruritus | 7 | 0 | 2 | 0 |
| Alopecia | 6 | 1 | 38 | 2 |
The following additional adverse reactions were observed in patients assigned to receive pemetrexed.
The safety of pemetrexed was evaluated in Study JMCH, a randomized (1:1), single-blind study conducted in patients with MPM who had received no prior chemotherapy for MPM. Patients received pemetrexed 500 mg/m2intravenously in combination with cisplatin 75 mg/m2intravenously on Day 1 of each 21-day cycle or cisplatin 75 mg/m2intravenously on Day 1 of each 21-day cycle administered until disease progression or unacceptable toxicity. Safety was assessed in 226 patients who received at least one dose of pemetrexed in combination with cisplatin and 222 patients who received at least one dose of cisplatin alone. Among 226 patients who received pemetrexed in combination with cisplatin, 74% (n=168) received full supplementation with folic acid and vitamin B12during study therapy, 14% (n=32) were never supplemented, and 12% (n=26) were partially supplemented.
Study JMCH excluded patients with Karnofsky Performance Scale (KPS) of less than 70, inadequate bone marrow reserve and organ function, or a calculated creatinine clearance less than 45 mL/min. Patients unable to stop using aspirin or other non-steroidal anti-inflammatory drugs were also excluded from the study.
The data described below reflect exposure to pemetrexed in 168 patients that were fully supplemented with folic acid and vitamin B12. Median age was 60 years (range 19 to 85 years); 82% were men; 92% were White, 5% were Hispanic or Latino, 3.0% were Asian, and <1% were other ethnicities; 54% had KPS of 90-100. The median number of treatment cycles administered was 6 in the pemetrexed/cisplatin fully supplemented group and 2 in the pemetrexed/cisplatin never supplemented group. Patients receiving pemetrexed in the fully supplemented group had a relative dose intensity of 93% of the protocol-specified pemetrexed dose intensity. The most common adverse reaction resulting in dose delay was neutropenia.
Table 6 provides the frequency and severity of adverse reactions ≥5% in the subgroup of pemetrexed-treated patients who were fully vitamin supplemented in Study JMCH. Study JMCH was not designed to demonstrate a statistically significant reduction in adverse reaction rates for pemetrexed, as compared to the control arm, for any specified adverse reaction listed in the table below.
aIn Study JMCH, 226 patients received at least one dose of pemetrexed in combination with cisplatin and 222 patients received at least one dose of cisplatin. Table 6 provides the ADRs for subgroup of patients treated with pemetrexed in combination with cisplatin (168 patients) or cisplatin alone (163 patients) who received full supplementation with folic acid and vitamin B12during study therapy. | ||||
bNCI CTCAE version 2.0 | ||||
Adverse Reactionb | Pemetrexed /cisplatin (N=168) | Cisplatin (N=163) | ||
All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | |
Laboratory | ||||
Hematologic | ||||
| Neutropenia | 56 | 23 | 13 | 3 |
| Anemia | 26 | 4 | 10 | 0 |
| Thrombocytopenia | 23 | 5 | 9 | 0 |
Renal | ||||
| Elevated creatinine | 11 | 1 | 10 | 1 |
| Decreased creatinine clearance | 16 | 1 | 18 | 2 |
Clinical | ||||
Eye Disorder | ||||
| Conjunctivitis | 5 | 0 | 1 | 0 |
Gastrointestinal | ||||
| Nausea | 82 | 12 | 77 | 6 |
| Vomiting | 57 | 11 | 50 | 4 |
| Stomatitis/pharyngitis | 23 | 3 | 6 | 0 |
| Anorexia | 20 | 1 | 14 | 1 |
| Diarrhea | 17 | 4 | 8 | 0 |
| Constipation | 12 | 1 | 7 | 1 |
| Dyspepsia | 5 | 1 | 1 | 0 |
Constitutional Symptoms | ||||
| Fatigue | 48 | 10 | 42 | 9 |
Metabolism and Nutrition | ||||
| Dehydration | 7 | 4 | 1 | 1 |
Neurology | ||||
| Sensory neuropathy | 10 | 0 | 10 | 1 |
| Taste disturbance | 8 | 0 | 6 | 0 |
Dermatology/Skin | ||||
| Rash | 16 | 1 | 5 | 0 |
| Alopecia | 11 | 0 | 6 | 0 |
The following additional adverse reactions were observed in patients receiving pemetrexed plus cisplatin:
Table 7 provides the results of exploratory analyses of the frequency and severity of NCI CTCAE Grade 3 or 4 adverse reactions reported in more pemetrexed-treated patients who did not receive vitamin supplementation (never supplemented) as compared with those who received vitamin supplementation with daily folic acid and vitamin B12from the time of enrollment in Study JMCH (fully-supplemented).
aNCI CTCAE version 2.0 | ||
Grade 3-4 Adverse Reactions | Fully Supplemented Patients N=168 (%) | Never Supplemented Patients N=32 (%) |
| Neutropenia | 23 | 38 |
| Thrombocytopenia | 5 | 9 |
| Vomiting | 11 | 31 |
| Febrile neutropenia | 1 | 9 |
| Infection with Grade 3/4 neutropenia | 0 | 6 |
| Diarrhea | 4 | 9 |
The following adverse reactions occurred more frequently in patients who were fully vitamin supplemented than in patients who were never supplemented:
- hypertension (11% versus 3%),
- chest pain (8% versus 6%),
- thrombosis/embolism (6% versus 3%).