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Cisplatin-carboplatin therapy in extensive non-small cell lung cancer: A cancer and leukemia group B study
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(NSCLC) were treated with epirubtcin 135-150 me/m* every 3 weeks. There were 6 partial responses. Randomised studies should reveal whether and how incorporationof epirubicin into combinationchemotherapy can enhance outcome in advanced NSCLC.
Recent advances in etoposide therapy for non-small cell lung cancer Bonomi P. Secrion of Medical Oncology, Rush Uniwrsiry Medicaf Center, 1725 Wesr Harrison. Suife 830, Chicago, IL 60612. Cancer 1991;67:Suppl254-9.
Non-small cell lung cancer (NSCLC) continuesto be a major health problem in the US. In l99O, approximately 120,OOOnew cases will be diagnosed, and the majority of these patients will have either unresectablediseaseor resecteddisease that has a relatively low chance of beingcured. A variety of chemotherapytreatmentshave beenevaluated in patients with advanced NSCLC. The objective of this review is to summarize the results of the chemotherapy trials in Stage III and IV NSCLC patients.
Etoposide in the management of non-small cell lung ePncer RuckdeschelJC. Division of Medical Oncology. Albany Medical College, A-167. Albany, NY 12208. Cancer 1991;67:Suppl2SO-3. Etoposide is a phase-specific, schedule-dependentderivative of podophyllotoxintha1appearsto act by inhibiting DNA-topoisomerase II. Early ln-eclinicalwork demimsuatedsharpactivityin mouseleukemias and possiblesynergy with cisplatin. As a single agent (either orally or intravenously), it demonstratedlimited benefit in non-small cell lung cancer (NSCLC), with responserates around 10% In combinationwith cisplatin, it has become a mainstay of chemotherapeuticefforts, either as primary therapy or in conjunctionwith radiation. Responserates in advanced diseaseaverage around 30%. climbing IO more than 50% in patientswith Stage IIIA or IIIB disease.More recent work suggeststhat theissueoftheuuesynergyofetoposidewithcisplatininNSCLCneeds reassessment.The relative roles of etoposide and cisplatin in the combination are unclear, as several sludiesconflict. Pharmacokinetic data suggestthat multiple daily fractions of etoposideare superior to prolongedinfusions,warranting several future trials. Thecurrent major role for etoposideplus cisplatin would appear to be in muldmodality and/or surgery. Several other agents have been studied with etoposide or etoposideplus cisplatin (mitomycin. vindesine,doxorubicin. cyclophosphamide,ifosfamide,andcarboplatin).but it isunclearwhetherthe addition of any of them offers any responseor survival advantage. A randomized trial to compare intravenous and oral etoposide in combination with cisphtin for the treatment of small cell lung cancer Johnson DH. Ruckdeschel JC. Keller JH, Lyman GH. Kallas GJ, Macdonald J et al. Division of Medical Oncology, Vanderbilt Universiry, NashviNe. TN. Cancer 1991;67:Suppl 245-9. In a randomized multi-center s1udy.83 palients wilh small cell lung cancer were randomly assignedto trcalment with cisplatin 100 mg/m’ intravenously(IV) day 1 and etoposide 120 mp/m’IV days 1.2. and 3 or cisplatin 100 mg/m’IV day 1and ecoposide120 mg/m’IV day 1 and 240 me/m’ orally days 2 and 3. Both regimens were repeated every 4 weeks. Prior to randomization, patients were Watified by extent of disease, performance status, and gender. A total of 41 patients were randomly assigned to the parentcral treatment only regimen, and 42 patienls received cisplatin and IV/oral etoposide therapy. Both treatment arms were comparableregarding patient characteristics.Limited disease(LD) patientsconstinued 52% and 49% of tbe patient population for the oral and IV etoposide regimens, respectively. The overall complete response(CR) and partial response(PR) rate was 50% (95% confidence interval [Cl] 35% to 65%) for the oral etoposlde regimen and 59% (95% CI 44% 10 74%) for the IV etoposide regimen (P = 0.438). For both regimens,55% of the LD patientsachieved either CR or PR. Time to progression and survival were comparable for both treatment arms. Hematologic toxicity was comparable in both treatmentarms, with 80% of patientsexperiencing grade 3 or4 neutropenia or thmmbocytopcnia.Moderate to severe anemia and weight loss were more predominantwith the IV than with me oral regimen.
Current status of etoposide in tbe management of small cell lung cancer JohnsonDH, HainsworthJD, Hande KR, Greco FA. Division ofhfedlml Oncology, Deparmenr of Medicine, Vanderbilt Universiry. Nashville. TN 37232-5536. Cancer 1991;67:Suppl 2314. Etoposide is a schedule-dependentdrug with excellent activity againstsmall cell lung cancer (SCLC). Single-agentetoposideachieves overall response rates ranging from 15% to 84%. depending on the schedule of drug administrationand the characteristicsof the tteated population.The mute of etoposideadministration(iniravenous versus oral) has little impact on responserate, provided appropriate dose adjustmentsare made for oral therapy. In combination with other active agents, etoposidehas proven particularly effective in the management of SCLC.Etoposidecan bcsubstituteddordoxorubicinorvincristine in the cyclophosphamide,doxorubicin, and vincristine (CAV) regimen without lossofefficacy.Theetoposideandcisplastin(EP)combination is thought to be synergisticand has proven to be an effective salvage regimen for CAV failures. A regimen that alternatesCAV and EP has been found by someinvestigatorsto be modestlymore effective against SCLC 1han CAV alone; however, EP alone may be as useful as an alternating regimen. Most studies to date have demonstratedthat EP induction is at least as cffec1ive as any other standard induction regimen. However, EP has me potentialadvantageof being more easily integrated with thoracic radiation therapy (RT). This is particularly importantin limited-diseasepatienls: two recent pilot studiesemploying EP induclion with hyperfractionated thoracic RT yielded 2-year survival rates of greater than 50%. These promising results are being evalualed further in an ongoing Phase III trial in the United States. The available data indicate ma1 etoposide is one of the most active agents against SCLC and therefore should be included as a component of induction therapy in all patients. New schedulesof etoposideadministration warrant further study.
Cisptatincnrboplatin therapy in extensivenon-smallcelt lung cancer: A cancer and leukemia group B study KreismaoH.GoutsouM, ModeasC,GrazianoSL.CostanzaME.Green MR. Pubnonory Division. Sir Morrimer B. Davis-Jewish General Hospital,
3755 Cole St Catherine
Road, Momreal,
Que. H3T IE2.
EIU
J Cancer 1990;26:1057-60. The response10 cisplatin in non-small cell lung cancer (NSCLC) is limited by the renal and neurological toxicities of this agenl. Carboplatinhasmodestactivityin NSCLC and whengiven inconventional doseshasadifferent spectrumof toxicity. Bothdrugswereadministered to 76 eligible patients with advanced NSCLC. No patient had be-en previously treated wilh chemotherapy. Cisplatin SO mg/m’ and carboplatin 350 mg/m* were administered every 28 days until disease progressionoccurred. There was 1 complete responseand the overall responserate among the 68 evaluable for responsepatients was 13%. Neither histological subtype nor initial performance status was a significantfactor influencingresponse.Median survivalwas 5.1 months with significantdifferences basedon initial performancestatusbut not on histological subtype. Severe or life-threamning Ieukopenia and thrombocytopeniaoccurred in 23% and 36% of the 76 patients,respectively. There were 2 toxic deaths. 1each due to infection and haemorrhage. The efficacy of this combination is not different from that of carboplatin alone, and the combination may be of greater bettent in patientswith more responsivetumours ihan NSCLC. Combination chemotherapy of limited-stage small-cell lung cancer. A controlled trial on 221 patients comparing two alternating regimens Osterlind K, Hansen M, Hirsch FR, Dombemowsky P, Sorenson S, PedersenAG et al. Deparmenf of Oncology, Finsen Ins~irvvlRigshospitalet. DK-2100 Copenhagen. Ann Gncol 1991;2:41-6. The outcomeof two differencalternating regimensof chemotherapy was investigatedin a prospeclivecontrolledtrial in limited-stagesmallcell lungcancer(SCLC). Both regimenscomprisedcyclophosphamide, lomustine. vincrisline, mcthotrexatc, doxorubicin and etoposide administered in different schedules. The investigative regimen (B) included simultaneousadministrationof cyclophosphamide+ lomustine alternating with cyclophosphamidc+ doxorubicin,and with doxorubi-
(NSCLC) were treated with epirubtcin 135-150 me/m* every 3 weeks. There were 6 partial responses. Randomised studies should reveal whether and how incorporationof epirubicin into combinationchemotherapy can enhance outcome in advanced NSCLC.
Recent advances in etoposide therapy for non-small cell lung cancer Bonomi P. Secrion of Medical Oncology, Rush Uniwrsiry Medicaf Center, 1725 Wesr Harrison. Suife 830, Chicago, IL 60612. Cancer 1991;67:Suppl254-9.
Non-small cell lung cancer (NSCLC) continuesto be a major health problem in the US. In l99O, approximately 120,OOOnew cases will be diagnosed, and the majority of these patients will have either unresectablediseaseor resecteddisease that has a relatively low chance of beingcured. A variety of chemotherapytreatmentshave beenevaluated in patients with advanced NSCLC. The objective of this review is to summarize the results of the chemotherapy trials in Stage III and IV NSCLC patients.
Etoposide in the management of non-small cell lung ePncer RuckdeschelJC. Division of Medical Oncology. Albany Medical College, A-167. Albany, NY 12208. Cancer 1991;67:Suppl2SO-3. Etoposide is a phase-specific, schedule-dependentderivative of podophyllotoxintha1appearsto act by inhibiting DNA-topoisomerase II. Early ln-eclinicalwork demimsuatedsharpactivityin mouseleukemias and possiblesynergy with cisplatin. As a single agent (either orally or intravenously), it demonstratedlimited benefit in non-small cell lung cancer (NSCLC), with responserates around 10% In combinationwith cisplatin, it has become a mainstay of chemotherapeuticefforts, either as primary therapy or in conjunctionwith radiation. Responserates in advanced diseaseaverage around 30%. climbing IO more than 50% in patientswith Stage IIIA or IIIB disease.More recent work suggeststhat theissueoftheuuesynergyofetoposidewithcisplatininNSCLCneeds reassessment.The relative roles of etoposide and cisplatin in the combination are unclear, as several sludiesconflict. Pharmacokinetic data suggestthat multiple daily fractions of etoposideare superior to prolongedinfusions,warranting several future trials. Thecurrent major role for etoposideplus cisplatin would appear to be in muldmodality and/or surgery. Several other agents have been studied with etoposide or etoposideplus cisplatin (mitomycin. vindesine,doxorubicin. cyclophosphamide,ifosfamide,andcarboplatin).but it isunclearwhetherthe addition of any of them offers any responseor survival advantage. A randomized trial to compare intravenous and oral etoposide in combination with cisphtin for the treatment of small cell lung cancer Johnson DH. Ruckdeschel JC. Keller JH, Lyman GH. Kallas GJ, Macdonald J et al. Division of Medical Oncology, Vanderbilt Universiry, NashviNe. TN. Cancer 1991;67:Suppl 245-9. In a randomized multi-center s1udy.83 palients wilh small cell lung cancer were randomly assignedto trcalment with cisplatin 100 mg/m’ intravenously(IV) day 1 and etoposide 120 mp/m’IV days 1.2. and 3 or cisplatin 100 mg/m’IV day 1and ecoposide120 mg/m’IV day 1 and 240 me/m’ orally days 2 and 3. Both regimens were repeated every 4 weeks. Prior to randomization, patients were Watified by extent of disease, performance status, and gender. A total of 41 patients were randomly assigned to the parentcral treatment only regimen, and 42 patienls received cisplatin and IV/oral etoposide therapy. Both treatment arms were comparableregarding patient characteristics.Limited disease(LD) patientsconstinued 52% and 49% of tbe patient population for the oral and IV etoposide regimens, respectively. The overall complete response(CR) and partial response(PR) rate was 50% (95% confidence interval [Cl] 35% to 65%) for the oral etoposlde regimen and 59% (95% CI 44% 10 74%) for the IV etoposide regimen (P = 0.438). For both regimens,55% of the LD patientsachieved either CR or PR. Time to progression and survival were comparable for both treatment arms. Hematologic toxicity was comparable in both treatmentarms, with 80% of patientsexperiencing grade 3 or4 neutropenia or thmmbocytopcnia.Moderate to severe anemia and weight loss were more predominantwith the IV than with me oral regimen.
Current status of etoposide in tbe management of small cell lung cancer JohnsonDH, HainsworthJD, Hande KR, Greco FA. Division ofhfedlml Oncology, Deparmenr of Medicine, Vanderbilt Universiry. Nashville. TN 37232-5536. Cancer 1991;67:Suppl 2314. Etoposide is a schedule-dependentdrug with excellent activity againstsmall cell lung cancer (SCLC). Single-agentetoposideachieves overall response rates ranging from 15% to 84%. depending on the schedule of drug administrationand the characteristicsof the tteated population.The mute of etoposideadministration(iniravenous versus oral) has little impact on responserate, provided appropriate dose adjustmentsare made for oral therapy. In combination with other active agents, etoposidehas proven particularly effective in the management of SCLC.Etoposidecan bcsubstituteddordoxorubicinorvincristine in the cyclophosphamide,doxorubicin, and vincristine (CAV) regimen without lossofefficacy.Theetoposideandcisplastin(EP)combination is thought to be synergisticand has proven to be an effective salvage regimen for CAV failures. A regimen that alternatesCAV and EP has been found by someinvestigatorsto be modestlymore effective against SCLC 1han CAV alone; however, EP alone may be as useful as an alternating regimen. Most studies to date have demonstratedthat EP induction is at least as cffec1ive as any other standard induction regimen. However, EP has me potentialadvantageof being more easily integrated with thoracic radiation therapy (RT). This is particularly importantin limited-diseasepatienls: two recent pilot studiesemploying EP induclion with hyperfractionated thoracic RT yielded 2-year survival rates of greater than 50%. These promising results are being evalualed further in an ongoing Phase III trial in the United States. The available data indicate ma1 etoposide is one of the most active agents against SCLC and therefore should be included as a component of induction therapy in all patients. New schedulesof etoposideadministration warrant further study.
Cisptatincnrboplatin therapy in extensivenon-smallcelt lung cancer: A cancer and leukemia group B study KreismaoH.GoutsouM, ModeasC,GrazianoSL.CostanzaME.Green MR. Pubnonory Division. Sir Morrimer B. Davis-Jewish General Hospital,
3755 Cole St Catherine
Road, Momreal,
Que. H3T IE2.
EIU
J Cancer 1990;26:1057-60. The response10 cisplatin in non-small cell lung cancer (NSCLC) is limited by the renal and neurological toxicities of this agenl. Carboplatinhasmodestactivityin NSCLC and whengiven inconventional doseshasadifferent spectrumof toxicity. Bothdrugswereadministered to 76 eligible patients with advanced NSCLC. No patient had be-en previously treated wilh chemotherapy. Cisplatin SO mg/m’ and carboplatin 350 mg/m* were administered every 28 days until disease progressionoccurred. There was 1 complete responseand the overall responserate among the 68 evaluable for responsepatients was 13%. Neither histological subtype nor initial performance status was a significantfactor influencingresponse.Median survivalwas 5.1 months with significantdifferences basedon initial performancestatusbut not on histological subtype. Severe or life-threamning Ieukopenia and thrombocytopeniaoccurred in 23% and 36% of the 76 patients,respectively. There were 2 toxic deaths. 1each due to infection and haemorrhage. The efficacy of this combination is not different from that of carboplatin alone, and the combination may be of greater bettent in patientswith more responsivetumours ihan NSCLC. Combination chemotherapy of limited-stage small-cell lung cancer. A controlled trial on 221 patients comparing two alternating regimens Osterlind K, Hansen M, Hirsch FR, Dombemowsky P, Sorenson S, PedersenAG et al. Deparmenf of Oncology, Finsen Ins~irvvlRigshospitalet. DK-2100 Copenhagen. Ann Gncol 1991;2:41-6. The outcomeof two differencalternating regimensof chemotherapy was investigatedin a prospeclivecontrolledtrial in limited-stagesmallcell lungcancer(SCLC). Both regimenscomprisedcyclophosphamide, lomustine. vincrisline, mcthotrexatc, doxorubicin and etoposide administered in different schedules. The investigative regimen (B) included simultaneousadministrationof cyclophosphamide+ lomustine alternating with cyclophosphamidc+ doxorubicin,and with doxorubi-