Topoccord 1/Topoccord 4 Adverse Reactions

In dose-finding studies involving 523 patients with relapsed ovarian cancer and 631 patients with relapsed small cell lung cancer, the dose limiting toxicity of topotecan monotherapy was found to be haematological. Toxicity was predictable and reversible. There were no signs of cumulative haematological or non-haematological toxicity.
The safety profile of topotecan when given in combination with cisplatin in the cervical cancer clinical studies is consistent with that seen with topotecan monotherapy. The overall haematological toxicity is lower in patients treated with topotecan in combination with cisplatin compared to topotecan monotherapy, but higher than with cisplatin alone.
Additional adverse events were seen when topotecan was given in combination with cisplatin, however, these events were seen with cisplatin monotherapy and were not attributable to topotecan. The prescribing information for cisplatin should be consulted for a full list of adverse events associated with cisplatin use.
The integrated safety data for topotecan monotherapy are presented as follows.
Adverse reactions are listed as follows, by system organ class and absolute frequency (all reported events). Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See table.)

Click on icon to see table/diagram/image

The frequencies associated with the haematological and non-haematological adverse events listed as follows represent the adverse event reports considered to be related/possibly related to topotecan therapy.
Haematological: Neutropenia: Severe (neutrophil count <0.5 x 10⁹/l) during course 1 in 55% of the patients with duration ≥7 days in 20% and overall in 77% of patients (39% of courses). In association with severe neutropenia, fever or infection occurred in 16% of patients during course 1 and overall in 23% of patients (6% of courses). Median time to onset of severe neutropenia was 9 days and the median duration was 7 days. Severe neutropenia lasted beyond 7 days in 11% of courses overall. Among all patients treated in clinical studies (including both those with severe neutropenia and those who did not develop severe neutropenia), 11% (4% of courses) developed fever and 26% (9% of courses) developed infection. In addition, 5% of all patients treated (1% of courses) developed sepsis (see Precautions).
Thrombocytopenia: Severe (platelets 25 x 10⁹/l) in 25% of patients (8% of courses); moderate (platelets between 25.0 and 50.0 x 10⁹/l) in 25% of patients (15% of courses). Median time to onset of severe thrombocytopenia was Day 15 and the median duration was 5 days. Platelet transfusions were given in 4% of courses. Reports of significant sequelae associated with thrombocytopenia including fatalities due to tumour bleeds have been infrequent.
Anaemia: Moderate to severe (Hb ≤8.0 g/dl) in 37% of patients (14% of courses). Red cell transfusions were given in 52% of patients (21% of courses).
Non-haematological: Frequently reported non-haematological effects were gastrointestinal such as nausea (52%), vomiting (32%), and diarrhoea (18%), constipation (9%) and mucositis (14%). The incidence of severe (Grade 3 or 4) nausea, vomiting, diarrhoea and mucositis was 4, 3, 2 and 1% respectively.
Mild abdominal pain was reported in 4% of patients.
Fatigue was observed in approximately 25% and asthenia in 16% of patients receiving topotecan. Severe (grade 3 or 4) fatigue and asthenia both occurred with an incidence of 3% respectively.
Total or pronounced alopecia was observed in 30% of patients and partial alopecia in 15% of patients.
Other severe events that were recorded as related or possibly related to topotecan treatment were anorexia (12%), malaise (3%) and hyperbilirubinaemia (1%).
Hypersensitivity reactions including rash, urticaria, angioedema and anaphylactic reactions have been reported rarely. In clinical studies, rash was reported in 4% of patients and pruritus in 1.5% of patients.