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No need for cranial irradiation in acute lymphoblastic leukaemia
Newsdesk No need for cranial irradiation in acute lymphoblastic leukaemia Results from a US study show that cranial irradiation can be avoided in children with acute lymphoblastic leukaemia (ALL). By use of a better method of risk classification, together with intensive intrathecal chemotherapy for high-risk patients and dexamethasone for post-remission therapy, Ching-Hon Pui and colleagues at St Jude Children’s Research Hospital, Memphis, TN, USA, have been able to limit the use of cranial irradiation to 12% of patients treated for ALL (Blood 2004; 104: 2690–96). This result compares with 22% of patients given radiotherapy in a previous study. The study involved 247 children younger than 18 years with newly diagnosed ALL. 117 children were classified as low risk (1–9 years with a leucocyte count of <50⫻109/L or a DNA index of >1·16) and 130 as high risk. Cranial irradiation was given only to patients with T-cell ALL and with a leucocyte count of 100⫻109/L or over, or a CNS-3 status (ie, five or
more blast cells in an atraumatic CNS sample or presence of cranial-nerve palsy). The study was designed to reduce risk of CNS relapse, use of cranial irradiation, and late complications such as second cancers and neurocognitive deficits. “The ability to omit cranial irradiation, while still achieving a high cure rate, would be an important breakthrough”, says Pui. “We chose dexamethasone because there is evidence that it is superior to prednisone and prednisolone, especially in control of CNS disease”, he explains. “We also broadened our risk classification to include more lower-risk children in post-remission treatment.” More importantly, says Pui, “it is apparent that patients with any leukaemic cells in their cerebrospinal fluid at diagnosis—even if these were introduced iatrogenically during traumatic lumbar puncture—are at higher risk of CNS relapse. Patients with this feature received more
intensive intrathecal therapy, and this approach might also have improved our CNS control”. “No CNS-directed therapy is completely safe, but cranial irradiation has the most late effects”, says David Webb (Great Ormond Street Hospital, London, UK). “This paper builds upon what various other groups have been saying—ie, that cranial irradiation has largely had its day, except for children with CNS leukaemia.” Overall event-free survival (81% at 5 years) and CNS relapse rate (3%) were very good, Webb adds. “The St Jude team has made huge contributions to the advance of knowledge of childhood leukaemia”, says Tim Eden (University of Manchester, UK). “The big challenges now facing us are to find out why patients otherwise defined as being low risk with conventional techniques still relapse and how we can make therapy applicable worldwide.” Dorothy Bonn
Dose-dense therapy shows promise in ovarian cancer Results of a new phase II trial have shown a weekly regimen of paclitaxel and carboplatin to be an effective treatment for patients with advanced ovarian cancer. Delegates at the 7th International Conference of Anticancer Research (Corfu, Greece; Oct 25–30, 2004) heard researchers from the Ovarian Cancer Study Group of the North-Eastern German Society for Gynaecologic Oncology (NOGGO) explain that a dose-dense regimen was just as effective as, and better tolerated than, the usual three-weekly regimen. Although the outlook for patients with ovarian cancer is poor, most will respond to firstline combination chemotherapy consisting of a platinum compound and a taxol. However, neurological and haematological toxic effects are common and can be doselimiting. Consequently, these factors often negatively affect patients’ quality of life. In a previous phase I trial, NOGGO found that patients with
Oncology Vol 5 December 2004
advanced ovarian cancer could tolerate weekly doses of paclitaxel and carboplatin (Gynecol Oncol 2002; 85: 321–326). “We then agreed that it
Rights were not granted to include this image in electronic media. Please refer to the printed journal. Platinum crystals make up valuable treatment.
would be appropriate to evaluate this dose-dense regimen in a phase II trial", says Oumar Camara, University of Jena, Germany. The study enrolled a total of 134 patients with advanced ovarian cancer (FIGO stage IIb–IV). Weekly paclitaxel and carboplatin were administered in three blocks; an initial
http://oncology.thelancet.com
dose of 100 mg/m2 paclitaxel had been defined in the earlier phase I trial. Two-thirds of the patients completed the full treatment plan, and in 75% of the evaluable patients, concentrations of the ovarian-cancer marker CA125 decreased after therapy. The researchers found the treatment was well tolerated, with fewer serious sideeffects than would have been expected in patients given the standard regimen. Furthermore, incidence of alopecia, diarrhoea, and changes in nail morphology were rare. “Our patients’ median postdiagnosis survival time of 43 months after a median 24-month follow-up interval was well within the range of published successful phase III trials, and we have concluded that weekly taxol can be safely combined with weekly carboplatin”, says Camara. “We now urgently need a phase III trial comparing the dose-dense [regimen] with standard treatment.” Clare Sansom
705
more blast cells in an atraumatic CNS sample or presence of cranial-nerve palsy). The study was designed to reduce risk of CNS relapse, use of cranial irradiation, and late complications such as second cancers and neurocognitive deficits. “The ability to omit cranial irradiation, while still achieving a high cure rate, would be an important breakthrough”, says Pui. “We chose dexamethasone because there is evidence that it is superior to prednisone and prednisolone, especially in control of CNS disease”, he explains. “We also broadened our risk classification to include more lower-risk children in post-remission treatment.” More importantly, says Pui, “it is apparent that patients with any leukaemic cells in their cerebrospinal fluid at diagnosis—even if these were introduced iatrogenically during traumatic lumbar puncture—are at higher risk of CNS relapse. Patients with this feature received more
intensive intrathecal therapy, and this approach might also have improved our CNS control”. “No CNS-directed therapy is completely safe, but cranial irradiation has the most late effects”, says David Webb (Great Ormond Street Hospital, London, UK). “This paper builds upon what various other groups have been saying—ie, that cranial irradiation has largely had its day, except for children with CNS leukaemia.” Overall event-free survival (81% at 5 years) and CNS relapse rate (3%) were very good, Webb adds. “The St Jude team has made huge contributions to the advance of knowledge of childhood leukaemia”, says Tim Eden (University of Manchester, UK). “The big challenges now facing us are to find out why patients otherwise defined as being low risk with conventional techniques still relapse and how we can make therapy applicable worldwide.” Dorothy Bonn
Dose-dense therapy shows promise in ovarian cancer Results of a new phase II trial have shown a weekly regimen of paclitaxel and carboplatin to be an effective treatment for patients with advanced ovarian cancer. Delegates at the 7th International Conference of Anticancer Research (Corfu, Greece; Oct 25–30, 2004) heard researchers from the Ovarian Cancer Study Group of the North-Eastern German Society for Gynaecologic Oncology (NOGGO) explain that a dose-dense regimen was just as effective as, and better tolerated than, the usual three-weekly regimen. Although the outlook for patients with ovarian cancer is poor, most will respond to firstline combination chemotherapy consisting of a platinum compound and a taxol. However, neurological and haematological toxic effects are common and can be doselimiting. Consequently, these factors often negatively affect patients’ quality of life. In a previous phase I trial, NOGGO found that patients with
Oncology Vol 5 December 2004
advanced ovarian cancer could tolerate weekly doses of paclitaxel and carboplatin (Gynecol Oncol 2002; 85: 321–326). “We then agreed that it
Rights were not granted to include this image in electronic media. Please refer to the printed journal. Platinum crystals make up valuable treatment.
would be appropriate to evaluate this dose-dense regimen in a phase II trial", says Oumar Camara, University of Jena, Germany. The study enrolled a total of 134 patients with advanced ovarian cancer (FIGO stage IIb–IV). Weekly paclitaxel and carboplatin were administered in three blocks; an initial
http://oncology.thelancet.com
dose of 100 mg/m2 paclitaxel had been defined in the earlier phase I trial. Two-thirds of the patients completed the full treatment plan, and in 75% of the evaluable patients, concentrations of the ovarian-cancer marker CA125 decreased after therapy. The researchers found the treatment was well tolerated, with fewer serious sideeffects than would have been expected in patients given the standard regimen. Furthermore, incidence of alopecia, diarrhoea, and changes in nail morphology were rare. “Our patients’ median postdiagnosis survival time of 43 months after a median 24-month follow-up interval was well within the range of published successful phase III trials, and we have concluded that weekly taxol can be safely combined with weekly carboplatin”, says Camara. “We now urgently need a phase III trial comparing the dose-dense [regimen] with standard treatment.” Clare Sansom
705