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Results from a US study show thatcranial irradiation can be avoided inchildren with acute lymphoblasticleukaemia (ALL). By use of a bettermethod of risk classification, togetherwith intensive intrathecal chemo-therapy for high-risk patients anddexamethasone for post-remissiontherapy, Ching-Hon Pui and collea-gues at St Jude Childrens ResearchHospital, Memphis, TN, USA, havebeen able to limit the use of cranialirradiation to 12% of patients treatedfor ALL (Blood 2004; 104: 269096).This result compares with 22% ofpatients given radiotherapy in a prev-ious study.

The study involved 247 childrenyounger than 18 years with newlydiagnosed ALL. 117 children wereclassified as low risk (19 years with aleucocyte count of 116) and 130 as highrisk. Cranial irradiation was givenonly to patients with T-cell ALL andwith a leucocyte count of 100109/Lor over, or a CNS-3 status (ie, five or

more blast cells in an atraumatic CNSsample or presence of cranial-nervepalsy).

The study was designed to reducerisk of CNS relapse, use of cranialirradiation, and late complicationssuch as second cancers and neuro-cognitive deficits. The ability to omit cranial irradiation, while stillachieving a high cure rate, would bean important breakthrough, saysPui. We chose dexamethasonebecause there is evidence that it issuperior to prednisone and pred-nisolone, especially in control of CNSdisease, he explains. We alsobroadened our risk classification toinclude more lower-risk children inpost-remission treatment. Moreimportantly, says Pui, it is apparentthat patients with any leukaemic cellsin their cerebrospinal fluid atdiagnosiseven if these wereintroduced iatrogenically duringtraumatic lumbar punctureare athigher risk of CNS relapse. Patientswith this feature received more

intensive intrathecal therapy, and thisapproach might also have improvedour CNS control.

No CNS-directed therapy is com-pletely safe, but cranial irradiation hasthe most late effects, says DavidWebb (Great Ormond StreetHospital, London, UK). This paperbuilds upon what various othergroups have been sayingie, thatcranial irradiation has largely had itsday, except for children with CNSleukaemia. Overall event-freesurvival (81% at 5 years) and CNSrelapse rate (3%) were very good,Webb adds.

The St Jude team has made hugecontributions to the advance of know-ledge of childhood leukaemia, saysTim Eden (University of Manchester,UK). The big challenges now facingus are to find out why patientsotherwise defined as being low riskwith conventional techniques stillrelapse and how we can make therapyapplicable worldwide.Dorothy Bonn

No need for cranial irradiation in acute lymphoblastic leukaemia

Results of a new phase II trial haveshown a weekly regimen of paclitaxeland carboplatin to be an effectivetreatment for patients with advancedovarian cancer. Delegates at the 7thInternational Conference of AnticancerResearch (Corfu, Greece; Oct 2530,2004) heard researchers from theOvarian Cancer Study Group of theNorth-Eastern German Society forGynaecologic Oncology (NOGGO)explain that a dose-dense regimen wasjust as effective as, and better toleratedthan, the usual three-weekly regimen.

Although the outlook for patientswith ovarian cancer is poor, most willrespond to firstline combinationchemotherapy consisting of a platinumcompound and a taxol. However,neurological and haematological toxiceffects are common and can be dose-limiting. Consequently, these factorsoften negatively affect patients qualityof life.

In a previous phase I trial,NOGGO found that patients with

advanced ovarian cancer could tolerateweekly doses of paclitaxel and carbo-platin (Gynecol Oncol 2002; 85:321326). We then agreed that it

would be appropriate to evaluate thisdose-dense regimen in a phase II trial",says Oumar Camara, University ofJena, Germany.

The study enrolled a total of134 patients with advanced ovariancancer (FIGO stage IIbIV). Weeklypaclitaxel and carboplatin wereadministered in three blocks; an initial

dose of 100 mg/m2 paclitaxel had beendefined in the earlier phase I trial.Two-thirds of the patients completedthe full treatment plan, and in 75% ofthe evaluable patients, concentrationsof the ovarian-cancer marker CA125decreased after therapy. The research-ers found the treatment was welltolerated, with fewer serious side-effects than would have been expectedin patients given the standard regimen.Furthermore, incidence of alopecia,diarrhoea, and changes in nailmorphology were rare.

Our patients median post-diagnosis survival time of 43 monthsafter a median 24-month follow-upinterval was well within the range ofpublished successful phase III trials,and we have concluded that weeklytaxol can be safely combined withweekly carboplatin, says Camara.We now urgently need a phase IIItrial comparing the dose-dense[regimen] with standard treatment.Clare Sansom

Dose-dense therapy shows promise in ovarian cancer

Platinum crystals make up valuable treatment.

Oncology Vol 5 December 2004 http://oncology.thelancet.com

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