highlighting cancer treatment reports

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January ChemotherapyResponse Rates... For Bladder Cancer Cancer Treatment Reports offers results from a number of Phase II and III clini cal trials. Yagoda and co-workers (Me morial Sloan-Kettering Cancer Center, New York, New York) report a 17 per cent partial response rate in 18 evaluable patients with bladder cancer. Thus while each agent is active alone and the combi nation is synergistic in mice, the clinical results with the combination are disap pointing. Similarly, Rodriguez and as sociates (University of Texas System Cancer Center, M.D. Anderson Hospi tal and Tumor Institute, Houston, Texas) report 19 percent (partial) re sponses in 27 patients with metastatic bladder cancer using a combination of VM-26 and adriamycin. Clearly, a broader range of active agents must be sought in further Phase II studies in blad der cancer. For Breast Cancer Two Phase II studies in metastatic breast cancer appear in this issue. Ahmann et al. (Mayo Clinic, Rochester, Minne sota) treated 32 patients with refractory metastatic breast cancer with either dianhydrogalactitol or ICRF-159 in a randomized study. No objective re sponses were noted. Mouridsen et al. (Copenhagen University Hospitals Gen tofle and Glostrup, Copenhagen, Den mark) conducted a randomized trial comparing cyclophosphamide alone versus a Cooper-type regimen. Twenty four evaluable patients were treated with cyclophosphamide as primary therapy with a 25 percent response rate, only one of which was complete. Of 27 patients receiving the combination, a response rate of 63 percent was observed with five complete responses. While hardly sur prising, this study again confirms the greater efficacy of drug combinations in advanced breast cancer. For Bronchogenic Cancer Treating 106 patients with advanced bronchogenic cancer, Samson et al. (Wayne State University, School of Medicine, Detroit, Michigan) describe results for the COMB (cyclophospha mide, vincristine, methyl-CCNU and bleomycin) regimen in various dose schedules and combinations. Only in small cell cancer were meaningful re sponses observed and these were not dif ferent quantitatively from other reported regimens. Alexander et al. (Stanford University School of Medicine, Stan ford, California) treated 23 patients with small cell cancer with either P0CC (pro carbazine, vincristine, cyclophospha mide, CCNU) or COMe (cyclophospha mide, vincristine, methotrexate) in a randomized study that included in volved-site radiotherapy. Similar re 188 CA—A CANCER JOURNAL FOR CLINICIANS Highlighting Cancer Treatment Reports Commentary on the January, 1977 (Volume61, Number1) issue John L. Ziegler, M.D. Associate Editor

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Page 1: Highlighting cancer treatment reports

January

ChemotherapyResponse Rates...

For Bladder Cancer

Cancer Treatment Reports offers resultsfrom a number of Phase II and III clinical trials. Yagoda and co-workers (Memorial Sloan-Kettering Cancer Center,New York, New York) report a 17 percent partial response rate in 18 evaluablepatients with bladder cancer. Thus whileeach agent is active alone and the combination is synergistic in mice, the clinicalresults with the combination are disappointing. Similarly, Rodriguez and associates (University of Texas SystemCancer Center, M.D. Anderson Hospital and Tumor Institute, Houston,Texas) report 19 percent (partial) responses in 27 patients with metastaticbladder cancer using a combination ofVM-26 and adriamycin. Clearly, abroader range of active agents must besought in further Phase II studies in bladder cancer.For Breast CancerTwo Phase II studies in metastatic breastcancer appear in this issue. Ahmann etal. (Mayo Clinic, Rochester, Minnesota) treated 32 patients with refractorymetastatic breast cancer with eitherdianhydrogalactitol or ICRF-159 in arandomized study. No objective responses were noted. Mouridsen et al.(Copenhagen University Hospitals Gen

tofle and Glostrup, Copenhagen, Denmark) conducted a randomized trialcomparing cyclophosphamide aloneversus a Cooper-type regimen. Twentyfour evaluable patients were treated withcyclophosphamide as primary therapywith a 25 percent response rate, only oneof which was complete. Of 27 patientsreceiving the combination, a responserate of 63 percent was observed with fivecomplete responses. While hardly surprising, this study again confirms thegreater efficacy of drug combinations inadvanced breast cancer.

For Bronchogenic CancerTreating 106 patients with advancedbronchogenic cancer, Samson et al.(Wayne State University, School ofMedicine, Detroit, Michigan) describeresults for the COMB (cyclophosphamide, vincristine, methyl-CCNU andbleomycin) regimen in various doseschedules and combinations. Only insmall cell cancer were meaningful responses observed and these were not different quantitatively from other reportedregimens. Alexander et al. (StanfordUniversity School of Medicine, Stanford, California) treated 23 patients withsmall cell cancer with either P0CC (procarbazine, vincristine, cyclophosphamide, CCNU) or COMe (cyclophosphamide, vincristine, methotrexate) in arandomized study that included involved-site radiotherapy. Similar re

188 CA—A CANCER JOURNAL FOR CLINICIANS

Highlighting

Cancer Treatment Reports

Commentary on theJanuary, 1977(Volume61, Number1) issue

John L. Ziegler, M.D.Associate Editor

Page 2: Highlighting cancer treatment reports

sponse rates (67 percent versus 70 percent) were observed, although P0CCtreated patients had slightly longer median survival. Eagan and colleagues(Mayo Clinic, Rochester, Minnesota)report results of several combinationregimens (VP16-cyclophosphamide,VP16-adriamycin and cyclophosphamide-adriamycin-cis-platinum) in 31patients with small cell cancer. A 77 percent overall response rate was reportedalthough only one patient achieved acomplete response. Responses did notdiffer by treatment regimen, and allcombinations were compatible with radiation therapy.For Hematologic MalignanciesA number of Phase II studies in hematologic malignancies are reported. Preisleret al. (Roswell Park Memorial Institute,Buffalo, New York) noted 13 completeremissions in 21 patients with acutemyelogenous leukemia treated with acytosine arabinoside (100 mg./m.2 continuous infusion, day one-seven) andadriamycin (30 mg./m.2 I.V., day onethree) combination. Patients who failedwere for the most part over 60 years ofage or had received prior therapy. Sullivan et al. (Royal Melbourne Hospital,Melbourne, Australia) describe a noveldose schedule for busulfan in patientswith chronic myeloid leukemia. Theytreated 17 patients with busulfan orallyin large doses (50 mg., 100 mg. or 200mg.) given over one to two days. NadirWBC occurred within two to six weeks(lowest, 900 per mm.3) and the meansurvival from diagnosis was 137 weeks(range 30-337 weeks). Further exploration of this type of dose-schedule mayoffer a reasonable alternative to chroniclow-dose busulfan with its attendant toxicity.

Results of “¿�CytoxanL-2 Protocol―

Garrett and associates report the resultsof the “¿�CytoxanL-2 Protocol― fromMemorial Sloan-Kettering Cancer Center. Forty-nine patients with advanced

non-Hodgkin's lymphoma were treatedwith a multi-drug sequential regimenwith response rates as follows: 64 percent (seven complete, two partial) in 14patients with DPDL, and 53 percent(seven complete, nine partial) in 30 patients with DHL. Two deaths occurredduring a period of profoundneutropenia. Responses are reflected byprolonged survival with 12 or 14 complete responders in continuous remission for three to 27 + months. O'Connellet al. (Mayo Clinic, Rochester, Minnesota) also report results of two adriamycm-containing combination regimens inadvanced lymphoma. The majority ofthe 42 patients had received prior radiation therapy and all had failed at leastone trial of chemotherapy. Responseswere noted in nine of 27 patients receiving BCNU, adriamycin and prednisone,and in five of 15 patients receivingVP16, adriamycin and prednisone. Bothregimens were well tolerated and appearto offer benefit to patients with good performance status who are refractory tostandard chemotherapy.

Negative Phase IIStudiesSeveral negative Phase II studies deserve mention. Evans et al. reporting forChildren's Cancer Group A, noted onlyone partial response using methylCCNU in 23 evaluable children with advanced, previously treated, neuroblastoma. In a Southwest Group study, 5-fluorouracil was given to 78 childrenwith advanced refractory cancer in atwice-weekly schedule. Seven partialresponses of brief duration were observed. Quagliana et al., reporting forthe Southwest Oncology Group, treated167 evaluable patients with various solidtumors with 5-azacytidine. Negligibleresponses were observed. This unfavorable result was echoed by Weiss and coworkers, who noted transient, minimalantitumor effects in 17 percent of patients with breast cancer and 21 percentof patients with lymphomas.

VOL. 27, NO. 3 MAY/JUNE 1977 189