Abstracts/Lung Cancer 10 (1993) 123-150 147

lines, NCI-H69/P (small cell). COR-L23/P (large cell). pad MORlP (adeaocarcinoma), were grown in increasing wnceatrations of cisplatio over a period of 6-9 months. This resulted in the development of sublines. H69/CPR, L23/CPR, and MOR/CPR which were 3- to E-fold resistnnt to cisplatin as determined by P 6day 3-(4,5- dimethylthiazol- Z-yl)-2,5diphenyltetrs?olium bromide zway. None of the resistam sublines showed P significant change in cellulu glutathione content or sensitivity tocadmiumcblori&(~indi~~rof~Uothi~eincoo~t), although changes in glutathiooe-S-transferwe activity were seen. The sublines each showed cross-resistance to melphalan. Cisplatin accumulation was unchaoged in H69/CPR. I.&fold reduced in L23/ CPR,snd2.0-foldrsducedioMOR/CPRcomptedwitbtheirnspective parent lines. In P pale1 of 10 small cell lung cancer cell lies. there was B 16-fold range of sensitivities to cisplatin. ‘Ilte panels have been used to examine cross- resistance between cisplatin, carboplatin. iproplatin, tetraplatin, sod P series of 10 novel ammine/amine dicarboxylate platinum(IV) compounds. Whereas H69/CPR pod MORlCPR showed little or no cross-resistance to my of the other compounds, L23lCPR was generally cross-resistant to all of them. In the panel of small cell lines, whereas the ranking of sensitivity to carboplatin and cisplatio were similar, each of the other compounds provided individual patterns ofsensitivity. There- alwaysa widenngeofsensitivities among the panel, ranging from S- toll-fold. Among thedicarboxylatecompounds, there was a great range of potencies, with two compounds (JM273 and JM274) being approximately 100-fold more pot& thao cisplatin.

Study of NCC-m-439 in patiwts with lung cancer Shiota T, Matsukam Y, Ikeda S, Hetakenaka R, Fooittso T. Kyoro Kmura Hospital, Chest Dimme Centw, 17 Yawdahirao, Kyofo 615. Long Cancer (The Netherlands) 1992;8:203-12

NCC-ST-439 is a glycoprotein recognized by P moooclonal antibody (ST439) which is obtained by using P human gastric cancer xenograph, ST+ as ao immuoogen. Using P Law Enzyme Kit from Nippon Kay&u, we measwed the serum level of NCC-ST-439 in 223 patients with long cancer, 344 patientswith benign lung diseaseaand 97 healthy adults. When weadopted acut-off level of4.5 U/ml forwomeo aged 50 years or more sod for mea of any age, nod 7.0 U/ml for women aged less than 50, the ovendl positive rates were 22.0% for the lung cancer patients, 7.0% for p&i&s with benign long diseases sod 3.1% for the healthy adults. ‘Ibe positive rate of the lung cancer patients was significantly higher than for patients with benign hmg diseases (P < 0.05). Accordiig to the histological type of lung cancer, the positive rates were 34.3% for 105 patients with adenoarcinoma, 9.8% for 68 patients with squmow cell carcinoma, sod 16.7% for 6 patients with large fell carcinoma. Clpssificotion of the lung cancer patients revealed positive rates for swum NCC-ST-439 of 0% for 40 Stage I patients, 8.3% in 12 Stage II patients, 12.5% io 48 Stage IIIA patients, 37.0% in 46 Stage IIIB patients. and 33.3% in 45 Stage IV patients. After we performed immunostaining for NCC-ST-439 using ST-439, positive immunoactivity was demonstrated mainly in the membrane of adamcarcinoma cells. NCC-ST439 thus seems to be a tomor associated marker in patients with lung adenowcinoma.

Randomized study with the pineal hormone melatonin versus supportivecarealoneinndvaneedno~leellllmg-re~istant to a fit-line chenotherppy containing cisplatin Lissoni P, Bami S, Ardizzoia A, Paolorossi F, Crispino S, Taocini G et al. Divisionedi Radiofempia, Ospedale S Germdo, I-2WS2 Monza. Gncology (Switzerland) 1992;49:3369.

At present. there is no effective medical therapy io metestatic nonsmall cell (NSC) lung cancer patients who progressed under a first- line chemotherapy containing cisplatio. Since recent data have demonstratedtheantineoplpsticpropertiesandthelackoftoxicityofthe pineal hormone melatonin (MLT), a randomized study was designed to evaluate the influence of an MLT treatment (10 mg/day orally at 7.00 p.m.) on the survival time at 1 year from the progression under chemotherapy in respect to supportive care alone in a group of m&static NSClungcancerpatient~~ whodidnotrespoodtoafirst-linechemotherapy containing cisplatin. The study includes 63 consecutive metestatic NSC lung cancer patients, who were randomized to receive MLT (n = 3 I) or

supportive care alone (n = 32). The percentage of both stabilizations of disease and survival at 1 year was significantly higher in patients treated with MLT than in those treated only with supportive care. No dmg- related toxicity was seen in patients treated with MLT, who, on tbe contrary, showed P significant improvement in performance status. This randomiredshdyshowsthstthepineslbormooeMLTmaybesuccessfully administered to prolong the survival time in mete&tic NSC long caocer patients who progressed under P first-line chemotherapy with cisplatin, for whom no other effective therapy is available up to now.

Random&d phase U triaI of High-Dose 4’-Etd-Doxorubicin +

K&tzE, Kc&c K, J&mJ. M&l Z, Pawlicki M, Ringwal~G et al. National Irwtitute of Oncology, Rath Gyorgy u 7-9, H 1122 B&pm. Oncology (Switzerland) 1992;49:32732.

One hundred and eleven previously untreated patients with ex(ensivesmpllcdlIungcpocerwaeinciudedinapmspectiverPndomitad study with the aim to asseas tbe efficacy and tolerance of bigbdose epirubicin (120 mgln?) in combiiation with either cyclophosphamide (800 mgld; arm 1) or cisplptin (60 mg/ m’: arm 2). Ninety-six patients were evahmble for response and toxicity and edditiooal 12 patients for toxicity only. Theoverall resporwrate (CR + PR) in ann 1 and Zwere 61.4 (27144) and 67.3% (35152). respectively. The own duration of remission was 4.4 months (arm I) and 4.9 months (arm 2). The - survival time was 6.6 months in ano 1 and 7.7 months in arm 2. WHO grade 4 toxicity was encountered in 25.5 and 15.8% of patients in arm 1 and 2, respectively. One case of cardiotoxicity resulting in the patient’s death was observed io arm 1. Both combinations showed considerable antitumor activity. Toxicity was acceptable.

Fhase II study of &h-dme epirubicia and etoposide in advanced noll-slmu cell IuqJ - Smit EF, Piers DA, Postmos PE. Drpamnenr of Puhtmmy Direare, University Hospiral. Free Univemify, De B&e&an 1117, 1007 MB Amteti. Eur J Cancer Part A Gee Top 1992;28: 1965-7.

25 coosecutive patients with advanced non-small cell lung c~ncer(NSCLC)wcretreotcdwithbighd~epirubicia(HDE) 135mg/ mZ nod etoposide 60 tug/m2 (days l-3) every 3 we&s. 121 courses, (median 6, range l-7). were administered and evaluable for toxicity: WHO grades III/IV leukocytopenin in 60136 (80%) courses, thmmbocytopenin in 1816 (20%) and gradea Ill111 anaemia in 31/6 (31%). Median (moge) left ventricular ejection fraction (LVEF) fell from 63% (53-73, n = 25) to 60% (48-73, n = 16) after 5 courses (P < 0.02). 2 patients had P drop of more thao 15 56 in LVEF with an epimbicin doseof mglm’. Apartfmm 1 patient who had tachycardia 6 months after the last course, no patient had congestive heart failure. Therewere2completesnd7partisl~spoases[totpI9/25(36%,95% confidence interval: 18-57.5%)]. Mediao survival is 31.8 (4.3-75) weeks. Combiiion HDE and etoposide in NSCLC offers no advantage over HDE alone sad is more toxic.

Radiotherapy

GmhamMV,GeitzLM,ByhardtR,AsbeUS,RoschMIII,UrtasunRC et al. Radiation Oncology Center, Washington Univ. Sdwolofbfcdicine. 4939Audubon.St.Louis, M063110. JNatICancerInst 1992;84:1731- 5.

Backgmund: Many stodies have sported differences in caocer incidence and survival between populations of Blacks end Whites. A 45 % higher death rate fmm loog cancer for BIack men sod a survival duration for Black p&ads with lung cancer that is generally shelter than that for White @as have also beat report& Purpose: Tile purpose of this study was to evallute whether race affects known prognostic factors for aoa-smrdIsslI lung cancer in Black versus White patients. This analysis attempts to de&mine which prognostic factors

148 Abstracts/ Lung Cancer IO (1993) 123-150

in four random&d pmqective ttiaIs conducted by the Radiation Thmppy Gncology Group (RTGG). The data wem pooled for . retrqective analysis of survival end prognostic t&tcws by race. Rent&~: Unitiate aneIy.sis showed significant diffaencos bshmm BI~~Whi(sswith~gudtossx,wei~tloss,histology,~RTOG Tstage(Pc.05). bet theonlycliaiully dgnificantdift&wtce(l’Y.Ol) was weight loss. Despite tbeue tiedings, ovezeIl SurviveI for Blacks and Whitesdidnotdi~significantIy(P = .67). MediaasuwivaIforBlac~ and Whites with I KamorsLy ~&nmaw statw(KPS)of9Oormore was 12.1 and 11.3 months, rsspsctivsly (P = .45). Swivel for Blacks andwhiteswitheKpSoflsss~9owps7.8~6.8mollths, rwpectivcly. Case of de& did not differ betwea the two races. For b&races, KPS, ege, sex, weight loss, and RTGG TandNstagsswere significant prognostic factors for muviwl (P< .Ol), but race was not P significant prognostic factor. Concltuion: Further shtdies of the differential in cancer survival for Blacks and Whi& may be indicated, but greeter impact may be achieved by addreesiag socioeconomic factors, lifestyle and oxupatioapl risk factors, health education, and access to adequate health care.

Rcsults of radietberapy with awire Intent In non-smaIl cell lung -.Ana&sIsdl3Opatie& Rein&s hf. Skolyswaki I. Kmcmiowski S. Rqecki W. Center of OncokJgy. M. sklcdowsko-clui~ Memorial Insl., ul. Gunmmka II, PL 31-115 K?akow. Stdde.nthslonLol 1992;168:573-8.

Behvea 1970 and 1985,130 patients were irradiated with curative inteat at the Cater of Gncology in Krakow. The bistologicpl diagnosis was squntous-cell cercinoma in 60.8% of patieots, adeaocarcinotne in 25.4 % of patimts and other non-s&l cell cancer in 13.8% of p&eats. Get of 130 irradiated patients 21.5% retiwed surgery, 26.2% were inoperable for medical reasxms, and 52.3% bed unrese~table tumors. Accotdiag to the UICC TNM 1987 classification, 62 (47.7%) patieate had early (stagea I end II) disease. The remaining 68 (52.3%) petieots bed stage IIl A cancer. Additional criteria for patients selection to radiotherapy with curative intent were: Kamofsky performance status SO, nod no respiratory insufficiency. All patients were treated with megavoltage radiation. Patients with stage I were treated by three isocatric beans. Tumor dose was 6ooo cGy in 24 fractions over five weeks. In patients with stage II and III A disease the Rdiothenpywprstutedwithhuo~lelopposedbeoms~co~ing primary lesion and mediastinum. Tbe dose of 4ooo cGy was given in 20 fractionsover fourweeks, followed bye ‘boost’doseof2OOOcGy in the tiactions over two weeks, delivered with three isoceatic beams. 54% of patiats were disease-free et the twelfth month, 24.6% at the 36th month, and 18.5 I of patients survived five years without evidence of cancer. AsigDificslltlybe(tersurvivnlhPsbeeaobservcd inpatientswith stages I and II, with Kamofsky performeece statis 70, and with complete mdiologicsl regression eight weeks atIer radiation therapy. The main cause of tilure of the VePtment were distant mstastase.s.

cIblicaI stqe II non-small cell lung cancer treated with radiation therapy alone: The signifianee of clinically staged ipsilatwel bilnr adenopathy (Nl disease) Rose&PI SA, Curme WJ Jr, Herbert SH, Hughes EN, Sandier HM, Stafford PM et al. UCSFIUCD Dept. of Radiation Onmlogy, UCD cancer Center, 4501 X Strrer, Sacramento. CA 95817. Cancer

1992;70:2410-7. &&ground. The prognosis of patiats with cliically staged

hilsr nodal involvement (Stage Nl) or clinical Stage II non-smnll cell lung cancer (NSCLC, Stage Tl-2NlMO) treated with radiation therapy (RT) done is not well established. Methods. Records of 758 ptieets with clinical Stage I-lI1 NSCLC treated with RT were reviewed. Sinty- two patients were identified with clinical Stage II NSCLC, and 126 patientsbadStageN1 disease.. Rwults.Tbemediaesurvival time(MST) of the 62 patieots with clinical Stage II disease was 17.9 months, with l-year, 2-y-, 3-y-r. and S-year overall actuarial survival ratea of 70%,33%, 20%. and 12%. respectively. Thesurvival of patientswith clinical StngendiseasewassignificaatlybetterthanthPt of389 patients

withclinicaIStageIIIAdisesse(MST, 11.3meetbs;P < O.O08)and267 patiettts with cliniul Stage IIIB disease (MST. 9.8 months; P = O.oaOS), but it was similar to that of 40 patie& with cliicrl Stage I lesions (MST, 15.0 months). Patients with performance statusa of O- 1 lived longer than those with a status of 2 or more (MST, 22.8 vemus 6.1 months; P < O.ooOl). Tbe mediae survival for pattieats with NO, NI, N2, and N3 disease was 13.7, 12.6, 10.9. and 9.1 months, respectively. PetimtswithStageNO-1 disease(MST, 13.2mcmths)had significantly improved MST compared with those with Stage N2-3 disease(MST, 10.3months). Conclusions. Thesurvivalofptieatswiti clinical Stage II NSCLC trerted with RT okme wea significantly better than that of those with clinical Stage IIIA or IIIB disease. It was comparable to that of patients with cliicpl Stage I lesions. The clinical staging of nodal involvement limited to the ipsileteral hilum does not neceswily portend P worse prognosis than that of patients with clinical Stage NO disease. The absence of clinically evideat Stage N2-3 disease is of significant predictive value. for patients with NSCLC treated with RT.

Endobmnchial irradiation with ‘Yr in the tmatment of malignant endobmnchIal obsbwtIon Par&lo JC, Waxman MI, ThmneBJ, B&x TA, Kqxcky WJ. Kanras City Pulmonary Clinic, 6420 Prospect, Kamu City, MO 64132. Chest 1992; 102: 1072-4.

From Jan 1, 1983 to April 30, 1989.32 patients umienveat 38 eedobmncbial treatments with ‘“Ir. bmocboscopicaIly inserted for treatment of endobmnchiaI obstructions seamday to bmnchogenic carcinoma. Thirty-four of the 38 treatments were far enough apart to allow separate twpotxse analysis. Thirty of tbe 34 patients were symptomatically improved or stable; 22 of 24 petients who could be evaluated roentgenographicelly showed improved or stable chest meetgenogmms, and tee of 12 ptieats evahuted bmncboscopically demonstrated improved patency of bmnchial lumen.

High dose rate bradtytbetnpy in patients with lecal maummxs after radiothesnpy of non-anaII cell lung cancer Sutecja G, Buis 0. Scheak~Kcming C, Van Zaedwijk N. Netherlands Camxrltwittue.Antotti wn~uwetthoekhttis. PLmkmlaan121.1066

CXAmt+?r&tn. Int J Radiat Cmcol Biol Phys 1992;24:551-3. Thirty-ooe patie& with recwreaceu of locaIly advanced

StngsI~lun~-werstrertcdwithhighdossntcbrpchythcnpy. All patimtn had previously received a full course extemaI beam irradietiw. AlI treatments were performed under topical aeaeahesia and took 6-14 mindependinpoethc~gtboftheIridium-192source. Thchigbdose ate bmchytherapy was c&ulated as 10 Gy at one cm from the source axis for each eessioe end this was reputed every 2 weeks to a maximum of three seasions. AI1 trentmmta were well tolerated and no immediate treatmeat &ted complicatioes were observed. Response ewIution 6

s&ival was i aad 3 months, *&wtively. AI1 ec&espomiers had ieitinlly presented with P T4N3 tumor. Tea patients died because of fatal pulmonary hemorrhages 2-24 weeks aRer bmchytherapy and three others died bxause of a breechid tishda. Bndobmnchial bmchytherapy appeare to be a vahmble treatment akemative for local paIliation. However, the relatively bigb number of complications at follow-up warrants further investigation to estlblish the optimaI benefit to be derived fromhigh dose rate hmcbytherapy treatmeaat of locally advuvxd stage III hunors.

Combined treatment modalities

Multimodal therapy of small cell lung - in TNM stages I through IIIa Muller LC, Salzer GM, Huber H, Prior C, Ebner I, Fmmmhold H et al. II Univ. Klinik fur Chirurgie, Abteilung fir 7horaxbirurgie. Anichstraw 35, A-6020 Innsbruck. Am llmrac Surg L992;54:493-7.

Since 1977, Innsbruck University Hospital has beeD employing a multimodal therapy concept for small cell bronchial carcioomas ie