16 THERAPY

Irradiation beneficial after conselVative breast cancer surgery

Postoperative radiotherapy appears to be beneficial when administered in addition to appropriate adjuvant drug therapy after conservative surgery for breast cancer, reports the Scottish Cancer Trials Breast Group.

In their study, 585 women (aged 28-70 years) undergoing such surgery for a ~ 4cm invasive, non fixed breast tumour received tamoxifen 20 mg/day if their tumour estrogen receptor (ER) concentrations were ~ 20 fmoVmg protein or if they had no ER assay result, or CMF antineoplastic therapy* if their tumour ER concentration was < 20 fmoVmg protein.

291 women also received radiotherapy to the residual breast tissue, with a boost to the tumour bed, and to the axillary and supraclavicular nodes, if the axillary nodes had not been surgically cleared. The other 294 women comprised an 'observation' group.

Loco-regional relapses reduced The major outcomes, after a median follow-up of

5.7 years, are shown in the table. All-cause mortality was not significantly different between the 2 groups. However, 18 loco-regional relapses (17 in the ipsilateral breast) occurred in the radiotherapy group, compared with 84 (72) in the observation group; 10 women in the fonner, and 34 in the latter group required mastectomy to control loco-regional relapse.

At study endpoint, or at death, 93.8% of women in the radiotherapy group and 81.3% of women in the observation group were free from loco-regional disease, with the breast preserved. * six 3-weeldy N bolus injections of cycIopIrosphanU rnJmg. methotre:mte 5()ng andjluorouraciJ (D) mgtm2 Forrest AP. S1.eWan ill, Evaington D, Scouisb ~ Trials Breast Group. RaDdomiscd controlled aiaI of conservation therapy for breast cancer: 6-year analysis oftbe Scottish aiaI. Lancet 348: 708-713, 14 Sep 1996 100<11<111

Fluorouracil enhanced by methotrexate in colorecta1 cancer

Low-dose methotrexate effectively enhances the efficacy of high-dose fluorouracil in patients with advanced or metastatic colorectal cancer, report researchers from the European Organization for Research and Treatment of Cancer - Gastrointestinal Tract Cancer Cooperative Group.

Inpharma-21 Sep 19M No.1OSS

3 10 such patients recei ved 4 courses of IV fluorouracil 60 mglkg over 48 hours at weekly intervals. This was followed by another 4 courses of therapy at 2-weekly intervals. Patients who had stable disease or who responded to therapy then continued treatment at 3-weekly intervals until disease progres­sion or unacceptable toxicity occurred. 154 of the patients were randomised to receive IV methotrexate 40 mg/m2 before the start of each fluorouracil infusion.

Outcomes in patients with colorectal cancer according to treatment group

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• eigntficandy differ..rt compered with fluorooracil-only recipienta •• comprieing ftuofOulWCil ."d low-doM m.tnot:ruate

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216 patients were evaluable for response. The partial response rate was significantly higher in fluorouracil + methotrexate recipients compared with fluorouracil-only recipients [see graph].

The median survival duration was 9.3 months in fluorouracil-only recipients compared with 12.5 months in fluorouracil + methotrexate recipients.

Both regimens were generally well tolerated. Blijbam G, Wagener T, Wlis J, de Greve J, Buset M, et aI. Modulation of high.oose infusional fluorouracil by low.oosc mcthotrex.ale in patients with

advanced or metastatic co1on:ctal cancer: final results of a randomized European Organization for Research and Treatment of~ srudy. Journal ofCJinicaJ

Oncology 14: 2266-2273, AU8 1996 _".

Antineoplastics + zalcitabine for AIDS-associated lymphoma

Low-dose antineoplastic therapy may be used with concomitant zalcitabine antiretroviral therapy in patients with AIDS-associated lymphoma, report US-based investigators. They note that lymphoma is a relatively late manifestation of mv infection that has been implicated in as many as 16% of all AIDS-related deaths.

The combined treatment approach achieved a complete remission* rate of 56% in the present study, which involved 25 evaluable men with newly diagnosed AIDS-related lymphoma and a mean CD4+ cell count of 164/mm3. They received combination treatment and supportive care measures as outlined in the table.

Antineoplastic therapy was repeated every 4 weeks for a maximum of 6 cycles, or 2 cycles beyond documentation of complete remission. Patients with CNS lymphoma, active intercurrent infection and

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THERAPY

Kamofsky performance status of less than 50% were excluded from the study.

Median survival of 8.1 months Median survival duration for all 25 patients was

8.1 months. Six of the 14 patients who achieved complete remission remained alive and disease-free at a median of 47.1 months. and the median overall survival time for complete responders was 29.2 months. Five of 14 complete responders relapsed within 23 months of completion of antineoplastic therapy and 4 of these patients died. Five patients achieved partial remission.

No significant neurotoxicity or other adverse events occurred with the combined regimen. * Complete remission was defined as the complete disappearance of all cliniaJIly derectable moJjgnant disease without development of new lesions for at Ieost 4 weekf. Levne AM, Tulpule A, Espina B, Boswell W, Buckley J. ct aI. Low dose mcthouexate, bleomycin, doxorubicin, cyclopbospbamide, vincristine, and dexamethasone with zalcitabiDc in pa1ients with acquired immunodeficiency

syndrome·related Iympboma: effect on human immunodeficiency virus and serum interleukin-6levels over time. Cancer 78: 517·526, I Aug 1996 _II Better quality of response with tretinoin + idarubicin in APL

Treatment with tretinoin and idarubicin appears to induce better quality complete remission in patients with acute promyelocytic leukemia (APL) than that which has previously been achieved with tretinoin alone, say Italian researchers.

In their pilot study, 20 patients aged 6-67 years who had newly diagnosed APL associated with the t(15,17) chromosomal translocation, received induction therapy with oral tretinoin [all-trans-

0156-2703.'!1611~171$O1.000 Ad .. Im.matlonal Umltlld 1l1li6. All rights ,.....,.

retinoic acid] 45 mglm2/day for up to 60 days, with IV idarubicin 12 mglm2/day administered on days 2, 4, 6 and 8. Patients who achieved a complete haematological remission then received 3 consol­idation courses comprising cytarabine, mitoxantrone. etoposide, idarubicin and thioguanine. Three patients subsequently underwent autologous bone marrow transplantation and 1 patient received maintenance treatment with mercaptopurine and methotrexate.

Complete haematological remission in 90% Complete haematological remission was achieved

in 18 patients after tretinoin and idarubicin therapy. The remaining 2 patients died during induction therapy.

Four of the 18 patients who received consolidation therapy relapsed after 4-23 months; 3 of these patients were treated with tretinoin and entered a second complete remission, while the remaining patient died.

After a median follow-up of 27 months for the surviving 17 patients, the Kaplan Meier estimates for overall survival rate and event-free survival rate were 85% and 69%, respectively.

The researchers believe that the combination of tretinoin and idarubicin reduced the toxicity that would be expected if either drug was given alone. including a reduction in the incidence of the retinoic acid syndrome and prevention of exacerbation of coagulopathy.

Importance of molecular remission A complete molecular remission (i.e. loss of the

PML-RARa hybrid gene on reverse transcription­polymerase chain reaction analysis) was achieved in 75% of evaluable patients at the completion of induction therapy, and by 90% of evaluable patients at the completion of consolidation therapy.

Long-term complete remission was shown to be associated with loss of the PML-RARa hybrid gene, while those patients who remained positive for the gene were at high risk of relapse. The researchers note that in contrast to the results of this study, previous studies of treatment with tretinoin alone have shown that patients have remained positive for the PML-RARa hybrid gene.

Avvisati G, La Coco F, Divc:rio D , Falda M, Ferrara F, ct aI. AIDA (all-trans

retinoic acid + idarubicin) in IICwly diagDosed acute promyelocytic 1eukania:

a Gruppo Italiano Malanie EmaIologicbe Maligne dell' Adulto (GIMEMA) Pilot Study. Blood 88: 1390-1398. IS Aug 1996 ....... ,.,

Inpharma- 21 8ep 1l1li6 No. 1055

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