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Hycamtin

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Hycamtin

Hycamtin

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Ovarian Cancer and Small Cell Lung Cancer

Data in the following section are based on the combined experience of 453 patients with metastatic ovarian carcinoma, and 426 patients with small cell lung cancer treated with HYCAMTIN. Table 1 lists the principal hematologic adverse reactions and Table 2 lists non-hematologic adverse reactions occurring in at least 15% of patients.

Table 1: Hematologic Adverse Reactions Experienced in ≥ 15% Ovarian Cancer and Small Cell Lung Cancer Patients Receiving HYCAMTIN

Hematologic Adverse Reaction Patients
(n = 879) % Incidence
Neutropenia
   < 1,500 cells/mm³ 97
   < 500 cells/mm³ 78
Leukopenia
   < 3,000 cells/mm³ 97
   < 1,000 cells/mm³ 32
Thrombocytopenia
   < 75,000/mm³ 69
   < 25,000/mm³ 27
Anemia
   < 10 g/dL 89
   < 8 g/dL 37

Table 2: Non-hematologic Adverse Reactions Experienced by ≥ 15% of Ovarian Cancer and Small Cell Lung Cancer Patients Receiving HYCAMTIN

Non-hematologic Adverse Reaction Percentage of Patients With Adverse Reaction (879 Patients)
All Grades Grade 3 Grade 4
Infections and infestations
  Sepsis or pyrexia/infection with neutropeniaa 43 NR 23
Metabolism and nutrition disorders
  Anorexia 19 2 < 1
Nervous system disorders
  Headache 18 1 < 1
Respiratory, thoracic, and mediastinal disorders
  Dyspnea 22 5 3
  Coughing 15 1 0
Gastrointestinal disorders
  Nausea 64 7 1
  Vomiting 45 4 1
  Diarrhea 32 3 1
  Constipation 29 2 1
  Abdominal pain 22 2 2
  Stomatitis 18 1 < 1
Skin and subcutaneous tissue disorders
  Alopecia 49 NA NA
  Rashb 16 1 0
General disorders and administrative site conditions
  Fatigue 29 5 0
  Pyrexia 28 1 < 1
  Painc 23 2 1
  Asthenia 25 4 2
NA = Not applicable.
NR = Not reported separately.
a Does not include Grade 1 sepsis or pyrexia.
b Rash also includes pruritus, rash erythematous, urticaria, dermatitis, bullous eruption, and maculopapular rash.
c Pain includes body pain, back pain, and skeletal pain.

Nervous System Disorders

Paresthesia occurred in 7% of patients but was generally Grade 1.

Hepatobiliary Disorders

Grade 1 transient elevations in hepatic enzymes occurred in 8% of patients. Greater elevations, Grade 3/4, occurred in 4%. Grade 3/4 elevated bilirubin occurred in < 2% of patients.

Table 3 shows the Grade 3/4 hematologic and major non-hematologic adverse reactions in the topotecan/paclitaxel comparator trial in ovarian cancer.

Table 3: Adverse Reactions Experienced by > 5% of Ovarian Cancer Patients Randomized to Receive HYCAMTIN or Paclitaxel

Adverse Reaction HYCAMTIN
(n = 112)
Paclitaxel
(n = 114)
Hematologic Grade 3/4 % %
Grade 4 neutropenia ( < 500 cells/mm³) 80 21
Grade 3/4 anemia (Hgb < 8 g/dL) 41 6
Grade 4 thrombocytopenia ( < 25,000 plts/mm³) 27 3
Pyrexia/Grade 4 neutropenia 23 4
Non-hematologic Grade 3/4 % %
Infections and infestations
  Documented sepsisa 5 2
Respiratory, thoracic, and mediastinal disorders
  Dyspnea 6 5
Gastrointestinal disorders
  Abdominal pain 5 4
  Constipation 5 0
  Diarrhea 6 1
  Intestinal obstruction 5 4
  Nausea 10 2
  Vomiting 10 3
General disorders and administrative site conditions
  Fatigue 7 6
  Asthenia  5 3
  Painb 5 7
a Death related to sepsis occurred in 2% of patients receiving HYCAMTIN and 0% of patients receiving paclitaxel.
b Pain includes body pain, skeletal pain, and back pain.

Table 4 shows the Grade 3/4 hematologic and major non-hematologic adverse reactions in the topotecan/CAV (cyclophosphamide-doxorubicin-vincristine) comparator trial in small cell lung cancer.

Table 4: Adverse Reactions Experienced by ≥ 5% of Small Cell Lung Cancer Patients Randomized to Receive HYCAMTIN or CAV

Adverse Reaction HYCAMTIN
(n = 107)
CAV
(n = 104)
Hematologic Grade 3/4 % %
Grade 4 neutropenia ( < 500 cells/mm³) 70 72
Grade 3/4 anemia(Hgb < 8 g/dL) 42 20
Grade 4 thrombocytopenia ( < 25,000 plts/mm³) 29 5
Pyrexia/Grade 4 neutropenia 28 26
Non-hematologic Grade 3/4 % %
Infections and infestations
  Documented sepsisa 5 5
Respiratory, thoracic, and mediastinal disorders
  Dyspnea 9 14
  Pneumonia 8 6
Gastrointestinal disorders
  Abdominal pain 6 4
  Nausea 8 6
General disorders and administrative site conditions
  Fatigue 6 10
  Asthenia 9 7
  Painb 5 7
a Death related to sepsis occurred in 3% of patients receiving HYCAMTIN, and 1% of patients receiving CAV.
b Pain includes body pain, skeletal pain, and back pain.

Cervical Cancer

In the comparative trial with HYCAMTIN plus cisplatin versus cisplatin in patients with cervical cancer, the most common dose-limiting adverse reaction was myelosuppression. Table 5 shows the hematologic adverse reactions and Table 6 shows the non-hematologic adverse reactions in patients with cervical cancer.

Table 5: Hematologic Adverse Reactions in Patients with Cervical Cancer Treated with HYCAMTIN Plus Cisplatin or Cisplatin Monotherapya

Hematologic Adverse Reaction HYCAMTIN Plus Cisplatin
(n = 140)
Cisplatin
(n = 144)
Anemia
  All Grades (Hgb < 12 g/dL) 131 (94%) 130 (90%)
  Grade 3 (Hgb < 8-6.5 g/dL) 47 (34%) 28 (19%)
  Grade 4 (Hgb < 6.5 g/dL) 9 (6%) 5 (3%)
Leukopenia
  All Grades ( < 3,800 cells/mm³) 128 (91%) 43 (30%)
  Grade 3 ( < 2,000-1,000 cells/mm³) 58 (41%) 1 (1%)
  Grade 4 ( < 1,000 cells/mm³) 35 (25%) 0 (0%)
Neutropenia
  All Grades ( < 2,000 cells/mm³) 125 (89%) 28 (19%)
  Grade 3 ( < 1,000-500 cells/mm³) 36 (26%) 1 (1%)
  Grade 4 ( < 500 cells/mm³) 67 (48%) 1 (1%)
Thrombocytopenia
  All Grades ( < 130,000 cells/mm³) 104 (74%) 21 (15%)
  Grade 3 ( < 50,000-10,000 cells/mm³) 36 (26%) 5 (3%)
  Grade 4 ( < 10,000 cells/mm³) 10 (7%) 0 (0%)
a Includes patients who were eligible and treated.

Table 6: Non-hematologic Adverse Reactions Experienced by ≥ 5% of Patients with Cervical Cancer Treated with HYCAMTIN Plus Cisplatin or Cisplatin Monotherapya

Adverse Reaction HYCAMTIN Plus Cisplatin
(n = 140)
Cisplatin
(n = 144)
All Gradesb Grade 3 Grade 4 All Gradesb Grade 3 Grade 4
General disorders and administrative site conditions
  Constitutionalc 96 (69%) 11 (8%) 0 89 (62%) 17 (12%) 0
  Paind 82 (59%) 28 (20%) 3 (2%) 72 (50%) 18 (13%) 5 (3%)
Gastrointestinal disorders
  Vomiting 56 (40%) 20 (14%) 2 (1%) 53 (37%) 13 (9%) 0
  Nausea 77 (55%) 18 (13%) 2 (1%) 79 (55%) 13 (9%) 0
  Stomatitis-pharyngitis 8 (6%) 1 ( < 1%) 0 0 0 0
  Other 88 (63%) 16 (11%) 4 (3%) 80 (56%) 12 (8%) 3 (2%)
Dermatology 67 (48%) 1 ( < 1%) 0 29 (20%) 0 0
Metabolic-Laboratory 55 (39%) 13 (9%) 7 (5%) 44 (31%) 14 (10%) 1 ( < 1%)
Genitourinary 51 (36%) 9 (6%) 9 (6%) 49 (34%) 7 (5%) 7 (5%)
Nervous system disorders
  Neuropathy 4 (3%) 1 ( < 1%) 0 3 (2%) 1 ( < 1%) 0
  Other 49 (35%) 3 (2%) 1 ( < 1%) 43 (30%) 7 (5%) 2 (1%)
Infection-febrile neutropenia 39 (28%) 21 (15%) 5 (4%) 26 (18%) 11 (8%) 0
Cardiovascular 35 (25%) 7 (5%) 6 (4%) 22 (15%) 8 (6%) 3 (2%)
Hepatic 34 (24%) 5 (4%) 2 (1%) 23 (16%) 2 (1%) 0
Pulmonary 24 (17%) 4 (3%) 0 23 (16%) 5 (3%) 3 (2%)
Vascular disorders
  Hemorrhage 21 (15%) 8 (6%) 1 ( < 1%) 20 (14%) 3 (2%) 1 ( < 1%)
  Coagulation 8 (6%) 4 (3%) 3 (2%) 10 (7%) 7 (5%) 0
Musculoskeletal 19 (14%) 3 (2%) 0 7 (5%) 1 ( < 1%) 1 ( < 1%)
Allergy-Immunology 8 (6%) 2 (1%) 1 ( < 1%) 4 (3%) 0 1 (<1%)
Endocrine 8 (6%) 0 0 4 (3%) 2 (1%) 0
Sexual reproduction function 7 (5%) 0 0 10 (7%) 1 ( < 1%) 0
Ocular-visual 7 (5%) 0 0 7 (5%) 1 ( < 1%) 0
Data were collected using NCI Common Toxicity Criteria, v. 2.0.
a Includes patients who were eligible and treated.
b Grades 1 through 4 only. There were 3 patients who experienced Grade 5 deaths with investigatordesignated attribution. One was a Grade 5 hemorrhage in which the drug-related thrombocytopenia aggravated the event. A second patient experienced bowel obstruction, cardiac arrest, pleural effusion and respiratory failure which were not treatment related but probably aggravated by treatment. A third patient experienced a pulmonary embolism and adult respiratory distress syndrome; the latter was indirectly treatment-related.
c Constitutional includes fatigue (lethargy, malaise, asthenia), fever (in the absence of neutropenia), rigors, chills, sweating, and weight gain or loss.
d Pain includes abdominal pain or cramping, arthralgia, bone pain, chest pain (non-cardiac and nonpleuritic), dysmenorrhea, dyspareunia, earache, headache, hepatic pain, myalgia, neuropathic pain, pain due to radiation, pelvic pain, pleuritic pain, rectal or perirectal pain, and tumor pain.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials or listed in other sections of the prescribing information, the following reactions have been identified during postmarketing use of HYCAMTIN. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to HYCAMTIN.

Blood and Lymphatic System Disorders: Severe bleeding (in association with thrombocytopenia) [see WARNINGS AND PRECAUTIONS].

Immune System Disorders: Allergic manifestations, anaphylactoid reactions.

Gastrointestinal Disorders: Abdominal pain potentially associated with neutropenic colitis [see WARNINGS AND PRECAUTIONS].

Pulmonary Disorders: Interstitial lung disease [see WARNINGS AND PRECAUTIONS].

Skin and Subcutaneous Tissue Disorders: Angioedema, severe dermatitis, severe pruritus.

General Disorders and Administration Site Conditions: Inadvertent extravasation [see WARNINGS AND PRECAUTIONS].

Read the Hycamtin (topotecan hydrochloride) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

G-CSF

Concomitant administration of G-CSF can prolong the duration of neutropenia, so if G-CSF is to be used, do not initiate it until day 6 of the course of therapy, 24 hours after completion of treatment with HYCAMTIN.

Platinum and Other Cytotoxic Agents

Myelosuppression was more severe when HYCAMTIN, at a dose of 1.25 mg/m²/day for 5 days, was given in combination with cisplatin at a dose of 50 mg/m² in Phase 1 trials. In one trial, 1 of 3 patients had severe neutropenia for 12 days and a second patient died with neutropenic sepsis.

Greater myelosuppression is also likely to be seen when HYCAMTIN is used in combination with other cytotoxic agents, thereby necessitating a dose reduction. However, when combining HYCAMTIN with platinum agents (e.g., cisplatin or carboplatin), a distinct sequence-dependent interaction on myelosuppression has been reported. Coadministration of a platinum agent on day 1 of dosing with HYCAMTIN required lower doses of each agent compared to coadministration on day 5 of the dosing schedule for HYCAMTIN.

For information on the pharmacokinetics, efficacy, safety, and dosing of HYCAMTIN at a dose of 0.75 mg/m²/day on days 1, 2, and 3 in combination with cisplatin 50 mg/m² on day 1 for cervical cancer, see DOSAGE AND ADMINISTRATION, ADVERSE REACTIONS, CLINICAL PHARMACOLOGY, and Clinical Studies.

Read the Hycamtin Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 3/18/2014
This monograph has been modified to include the generic and brand name in many instances.

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