Group items tagged

We sought to systematically evaluate the evidence base for all new drugs and new indications for the treatment of solid tumours and haematological malignancies approved by the EMA in the five year period 2009-13

Three investigators (AP, EP, and EG) independently extracted data on and descriptively analysed the following trial features: characteristics of the participant population, study design (randomisation, crossover from experimental to control group, and blinding of investigators and participants), experimental and control groups, enrolment, primary and secondary endpoints, magnitude of benefit on survival and quality of life, and narrative interpretation of the findings

Only 18 of the 68 (26%) were supported by a pivotal study powered to evaluate overall survival as the primary outcome

From 2009 to 2013, the EMA approved use of 48 oncology drugs

Seventeen drugs were approved for treatment of haematological malignancies and 51 for treatment of solid tumours

Overall, 72 clinical trials supported the approval of 68 novel drug uses

Our scoring was limited to drugs for solid tumours

Among 68 cancer drug indications approved by the EMA in the period 2009-13, and with a median of 5.4 years’ follow-up, only 35 (51%) were associated with a significant improvement in survival (26/35) or quality of life (9/35) over existing treatment options, placebo, or as add on treatment

Only two of the 26 drugs shown to extend life also showed benefits on quality of life

33 (49%) had not shown any improvement on survival or quality of life

This systematic evaluation of oncology drug approvals by the EMA in 2009-13 shows that most of the drugs (39/68, 57%) entered the market without evidence of improved survival or quality of life

At a minimum 3.3 years after market entry, there was still no conclusive evidence that 33 of these 39 cancer drugs either extended or improved life

What are potential reasons for the paucity of drug approvals with demonstrable survival advantages over existing treatments?

Firstly, only 18 (26%) indications for use in our cohort were supported by trials in which extension of life was the primary outcome

None of the pivotal studies supporting oncology drug approvals from 2009 to 2013 included quality of life as a primary outcome measure

Most new oncology drugs authorised by the EMA in 2009-13 came onto the market without clear evidence that they improved the quality or quantity of patients’ lives

Non-recombinant urate oxidase (Uricozyme®)

recombinant urate oxidase (Rasburicase®)

urine alkalisation may induce calcium phosphate deposition

renal replacement therapy should be started on an emergency basis when hydration fails to produce a prompt metabolic improvement or when ARF develops

Up to 50% of patients with newly diagnosed multiple myeloma have renal failure and up to 10% require dialysis

renal ultrasonography remains the method of choice for investigating extra-renal obstruction

The relief of the obstruction, either by percutaneous nephrostomy or through a ureteral stent, is the cornerstone of treatment

TMA may be associated with the cancer itself, with cancer chemotherapy, or with allogeneic BMT

thrombotic microangiopathy (TMA)

it may be as high as 5%

Most of the cases occur in patients with solid tumours, the most common type being adenocarcinoma (stomach, breast and lung)

The pathophysiology of the TMA-malignancy association remains controversial, although many studies suggest an insult to the vascular endothelium

mitomycin C. Subsequently, TMA has been reported with many anti-cancer agents, including gemcita-bine, bleomycin, cisplatin, CCNU, cytosine arabinoside, daunorubicin, deoxycoformycin, 5-FU, azathioprine and interferon α

Plasma exchanges have been shown to improve prognosis in the general population of patients with TMA

Causative factors should be looked for and antihypertensive treatment given. Lastly, in the absence of guidelines, we believe that plasma exchange should be proposed in patients with severe cancer treatment-associated TMA

The most widely used protective measure is saline infusion to induce solute diuresis

During methotrexate infusion and elimination, fluids should be given to maintain a high urinary output and urinary alkalisation should be performed to keep the urinary pH above 7.5. Rescue with folinic acid (50 mg four times a day) should be started 24 hours after each high-dose metho-trexate infusion and serum methotrexate concentrations should be measured every day

cyclophosphamide and ifosfamide