Thalidomide in Combination with Idarubicin, Dexamethasone and Etoposide (TIDE) Is an Effective Oral Combination in Heavily Pre-Treated Myeloma Patients.
Authors: Linch Mark D. , Jenner Matthew W. , Dines Sharon , Davies Faith E. , Morgan Gareth J. 
Published: October 2019

Dexamethasone, thalidomide, etoposide and an antracycline have formed part of regimens such as DT-PACE which have demonstrated efficacy in previously treated patients with multiple myeloma. They are inpatient regimens which limit their usage in a palliative setting. We have designed an oral regimen incorporating these agents. The toxicity and efficacy data of this novel treatment are presented. Between October 2004 and May 2007 patients who had progressive myeloma or were intolerant of DT-PACE were treated with 100–200mg of thalidomide on days 1–21 and four days (D1–4) of 10mg/m2 idarubicin, 40mg dexamethasone and 50mg/m2 etoposide twice daily (TIDE). All agents were administered orally on a 21 day cycle for a maximum of 5 cycles. Aciclovir, co-trimoxazole and Lansoprazole were administered routinely and G-CSF was administered in the event of neutropenic fever and as secondary prophylaxis. Thromboembolism prophylaxis was not specified. Response was assessed using the international uniform response criteria for multiple myeloma. Toxicity was assessed using the CTCAE version 3.0. Efficacy data is presented as intention to treat. Nineteen patients received TIDE chemotherapy with a median age of 60 (range 36–70) and a male to female ratio of 11:8. Patients had a median of 3 (range 1–6) previous cycles and 18/19 patients had previous thalidomide. Patients received a median of 3 cycles (range 1–5) of TIDE. The most common grade 3/4 non-haematological toxicities were infection (8 patients), thromboembolism (3 patients), nephrotoxicity (2 patients), diarrhoea (1 patient) and peripheral neuropathy (1 patient). Grade 3–4 haematological toxicity occurred in 17/19 patients but 10/19 patients had grade 1–2 ‘toxicity’ at baseline. There were no recorded toxic deaths. Out of the 8 patients that suffered neutropenic fever, 7 experienced this on their 1st cycle resulting in treatment cessation in 3 patients. With prophylactic G-CSF or dose reduction, 3 of the remaining 4 patients did not get further neutropenic sepsis. In total 6 patients required a dose reduction and 17/19 patients had G-CSF. Seven patients were anti-coagulated from the beginning of this study; 2 were on Erythropoetin, 2 had previous thromboembolism and 3 were commenced at the clinicians discretion. None of the anti-coagulated patients went on to have a thromboembolic event. 18/19 patients were evaluable for response. The overall response rate was 42% (1CR, 7PR, 9SD and 1PD). The response rate to TIDE in patients who were intolerant of inpatient DT-PACE was the same as those that were treated with TIDE alone (50% vs 45%). The median progression free survival was 4 months (range 1–12) and the median overall survival was 8 months (range 1–31). In patients who responded to TIDE the median progression free survival was 7 months (range 3–12) and the median overall survival was 10 months (range 4–23). The TIDE regimen is able to induce responses in heavily pre-treated myeloma patients, including those taking thalidomide at the time of disease progression. Toxicities are acceptable but primary prophylactic G-CSF and anticoagulation should be contemplated. Consideration should also be given to using the TIDE regimen at an earlier stage in the disease process.