Adding Radiotherapy to CHOP Improves Results for Early- or Limited-Stage NHL

December 1, 2002

ORLANDO, Florida-Updateddata from two separate studiesratify earlier results showing thatfollowing CHOP (cyclophosphamide[Cytoxan, Neosar], doxorubicinHCl, vincristine [Oncovin],prednisone) with radiation improvesresults for patients with early-or limited-stage non-Hodgkin’slymphoma (NHL), according todata reported at the 43rd AnnualMeeting of the American Society ofHematology (abstract 3023) .

ORLANDO, Florida-Updateddata from two separate studiesratify earlier results showing thatfollowing CHOP (cyclophosphamide[Cytoxan, Neosar], doxorubicinHCl, vincristine [Oncovin],prednisone) with radiation improvesresults for patients with early-or limited-stage non-Hodgkin'slymphoma (NHL), according todata reported at the 43rd AnnualMeeting of the American Society ofHematology (abstract 3023) .The final results of E1484 showedthat radiotherapy was successful inconverting patients with limitedstagediffuse aggressive NHL whohad achieved partial response followingtreatment with CHOP tocomplete response. In a trial conductedby the Southwest OncologyGroup (SWOG), patients with early-stage aggressive NHL receivingCHOP plus radiotherapy continuedto realize survival advantages superiorto patients receiving CHOPalone at greater doses.New Results, Old System
In reporting the final results ofE1484, Sandra J. Horning, MD, ofStanford University in Californianoted that the study had "the advantageof mature follow-up, butthe disadvantage of outdated classification,"having been done beforethe International Prognostic Index(IPI) or the WHO and REAL classificationsbecame standard.Patient accrual and randomizationran from October 1984 to September1992. "The objectives of thisstudy," Dr. Horning explained,"were to determine the complete responserate and the toxicity ofCHOP for early-stage diffuse aggressivelymphoma, to compare the effectof involved field radiotherapyafter a CHOP-induced remissionwith end points of duration of response,survival, sites of relapse, andtoxicity, and lastly to determine theability of radiotherapy to convertpartial responders to complete responders."Predominantly Diffuse
Large-Cell Lymphomas

Most patients in the study (82%)had diffuse large-cell lymphoma. Tobe eligible, patients had to be in stageIE/II/IIE, or to have mediastinal, retroperitoneal,or bulky disease, definedas ≥ 10 cm if stage I.The vast majority of patients hada performance status of 0 to 1 andslightly less than one-third had bulkydisease. A total of 81% of patientshad fewer than three disease sites,according to the Ann Arbor classification.Stage I disease was presentin 31% (14% stage I, 17% stage IE)and the remainder had stage II disease.Extranodal disease was presentin 47% of patients (and in this studythe spleen was considered anextranodal site). The median age ofparticipants was 59 years.Patients were initially stratifiedbased on performance status, tumormass, and number of disease sites."Randomization was up front," Dr.Horning said. "Patients in both armsof the study received a full eight cyclesof CHOP. Those in arm 1 whoachieved a complete response wereobserved, whereas those in arm 2received 30 Gy of involved field radiation.Partial responders in eitherarm received 40 Gy of radiation".Among the 324 patients who completedall eight cycles of chemotherapy,the only four deaths were due toCHOP toxicity. Among the worsttoxicities, 33% were grade 3 and 45%were grade 4. Almost all toxicitieswere restricted to neutropenia.Conversions From Partial to
Complete Response

Among patients for whom responsedata were available, "215, or61%, achieved a complete remissionas defined in the protocol, with relativelynarrow confidence intervals,"Dr. Horning reported. "Note that28% of patients converted from partialresponse to complete responsewith the addition of radiation therapy,"she added.A smaller subset of patients actuallyreceived consolidation treatment.These were the 79 patients in arm 2who achieved complete response andwent on to receive 30 Gy of involvedfield radiation. In arm 1 there were93 patients who achieved completeresponse and were then observed.Partial responders numbered 71.Among those receiving consolidationtherapy, there was a 17% increasein failure-free survival at 5years and 15% at 15 years, Dr.Horning reported. Time-to-progressiondata showed only one relapseafter 6 years of treatment in eitherarm of the study."I think it is notable that 78% ofthe patients in the radiation therapyarm are still in remission or estimatedto be in remission at 15 years," Dr.Horning stated. Multiple regressionanalysis showed performance statusof 2 to 4 and more than three involvedsites to be statistically significant adversefactors for time to progression."Bulk, stage, extranodal disease, age,and gender were not statistically significant,"Dr. Horning said.Curves for overall survival diverged,came together, and againseparated somewhat at 15 years.There were no statistical differencesin overall survival. "This study doessuffer from a small number of patients,"Dr. Horning acknowledged."In conclusion, the complete responserate in this study was 61%after eight cycles of CHOP therapy.We found that 28% of partial respondersconverted to complete responderswith 40 Gy of involved fieldradiotherapy. Overall, inductionCHOP of eight cycles was relativelywell tolerated," Dr. Horning said.Important Difference Between
the Two Trials

Updated data from the SWOGtrial found that survival advantagesshown at 4.4 years median followupfor CHOP(3) (three cycles ofCHOP) plus radiation compared toCHOP(8) (eight cycles of CHOP)alone were essentially unchanged atabout 8.2 years. Overall survivalrates were 82% for CHOP(3) plusradiation vs 74% for CHOP(8). Failure-free survival rates were 76% forCHOP(3) plus radiation vs 67% forCHOP(8).Patients eligible for the SWOGtrial had biopsy-proven intermediate-or high-grade NHL, except lymphoblastic,according to Thomas P.Miller, MD, of Arizona Cancer Centerin Tucson. "The important differencebetween this trial and theone presented by Dr. Horning is thatnonbulky stage II and IIE, that is,patients with a single mass measuring10 cm or greater than one-thirdchest diameter, were ineligible, presumingthree cycles of CHOP wouldbe inadequate therapy."