Lipo-Dox Adverse Reactions

Summary of the safety profile: The most common undesirable effect reported was palmar-plantar erythrodysesthesia (PPE). The effects of PPE are mostly mild, but in some case, the effects of PPE are severe and life-threatening. PPE infrequently results in permanent treatment discontinuation. PPE is characterised by painful, macular reddening skin eruptions. In patients experiencing this event, it is generally seen after two or three cycles of treatment. Improvement usually occurs in one - two weeks, and in some cases, may take up to 4 weeks or longer for complete resolution. Pyridoxine at a dose of 50-150 mg per day and corticosteroids have been used for the prophylaxis and treatment of PPE. Other strategies to prevent and treat PPE, which may be initiated for 4 to 7 days after treatment with pegylated liposomal doxorubicin include keeping hands and feet cool, by exposing them to cool water (soaks, baths, or swimming), avoiding excessive heat/hot water and keeping them unrestricted (no socks, gloves, or shoes that are tight fitting). PPE appears to be primarily related to the dose schedule and can be reduced by extending the dose interval 1-2 weeks. However, this reaction can be severe and debilitating in some patients and may require discontinuation of treatment.
Stomatitis/mucositis and nausea were also commonly reported in breast/ovarian cancer patient populations, whereas the AIDS-KS Program (20 mg/m² every 2 weeks), myelosuppression (mostly leukopaenia) was the most common side effect. The PPE is also common adverse reaction for patients with multiple myeloma patients treated with pegylated liposomal doxorubicin plus bortezomib combination therapy. The most frequently medicine-related or treatment-emergent adverse events in combination therapy (Pegylated liposomal doxorubicin + bortezomib) are nausea, diarrhoea, neutropaenia, thrombocytopaenia, vomiting, fatigue, and constipation.
For All Patients: During treatment with pegylated liposomal doxorubicin, infusion-associated reaction is common adverse reaction for patients with solid tumor. The infusion-associated reactions are defined as following: allergic reaction, anaphylactoid reaction, asthma, face edema, hypotension, vasodilatation, urticaria, back pain, chest pain, chills, fever, hypertension, tachycardia, dyspepsia, dizziness, dyspnea, pharyngitis, rash, nausea, pruritus, sweating, injection site reaction and drug interactions. For patients with multiple myeloma receiving pegylated liposomal doxorubicin plus bortezomib, the infusion-associated recations are common. And for patients with AIDS-KS the infusion-associated reactions are also common which were characterized by flushing, shortness of breath, facial edema, headache, chills, back pain, tightness in the chest and throat, and/or hypotension. Permanent treatment discontinuation rates infusion-associated reaction are infrequently occurs. Very rarely, convulsions have been observed in relation to infusion reactions.
In all patients, infusion associated reactions occurred primarily during the first infusion. Usually, temporarily stopping the infusion could resolve these symptoms without further therapy. In nearly all patients could resume pegylated liposomal doxorubicin treatment after all symptoms have resolved without recurrence. After the first cycle of pegylated liposomal doxorubicin treatment finished, the infusion reactions rarely recurred. Infusion reactions rarely recur after the first treatment cycle with pegylated liposomal doxorubicin.
Myelosuppression associated with anaemia, thrombocytopaenia, leukopaenia, and rarely febrile neutropaenia, has been reported in pegylated liposomal doxorubicin-treated patients.
There was stomatitis reported in patients receiving continuous infusions of conventional doxorubicin HCl and was frequently reported in patients receiving pegylated liposomal doxorubicin. It did not interfere with patients completing therapy and no dosage adjustments are generally required, unless Stomatitis is affecting a patient's ability to eat. In the case, the dose interval by 1 to 2 weeks or reduce the dosage.
Treatment of standard doxorubicin HCl at cumulative doses of lifetime above 450mg/m² or at lower doses for patients with cardiac risk factors may increase the incidence of congestive heart failure. However, the incidence of clinically significant cardiac injury was very low in the solid tumor patients (including breast and ovarian cancers) receiving pegylated liposomal doxorubicin.
As with other DNA-damaging antineoplastic agents, secondary acute myeloid leukemias and myelodysplasias have been reported in patients having received combined treatment with doxorubicin. Therefore, any patient treated with doxorubicin should be kept under haematological supervision.
Although local tissue necrosis following extravasation of pegylated liposomal doxorubicin has been reported very rarely, but its irritant reaction should be considered. If any symptoms of extravasation occur (e.g., stinging, erythema), the infusion should be immediately terminated and restarted in another vein. The application of ice over the site of extravasation for approximately 30 minutes may be helpful in alleviating the local reaction. Pegylated liposomal doxorubicin should not be given by the route of intramuscular or subcutaneous.
The recurrence of skin reaction due to prior radiotherapy is very rarely seen in pegylated liposomal doxorubicin administration.
Following the marketing of pegylated liposomal doxorubicin, serious skin conditions including erythema multiforme, Stevens Johnson syndrome and toxic epidermal necrolysis have been reported very rarely.
In patients treated with pegylated liposomal doxorubicin, cases of venous thromboembolism, including thrombophlebitis, venous thrombosis and pulmonary embolism have been seen uncommonly. However, because patients with cancer are at increased risk for thromboembolic disease, a causal relationship cannot be determined.