188

MULTIMODALITY TREATMENT WITH MITOMYCIN C (M) CIBPLATlN (P) VlNBLASTINE 0’) NEOADJWANT CHEMCVHERAPY (MPV), SURGERY AND RADIUTHERAPY IN LOCALLY ADVANCED (IIIA AND ,,,B) NON SMALL CELL LUNG CANCER (NSCLO. CFfiyio, GSeresoli. A. Bolognesi. M. Ronzcmi, p. &mini*. G.Chicss*. A.Canena*,

Depmnmmt of Radiahemotbenw. ??Depanment of limmcic SurgeryJrtituto Scientifico San Raffaele.Milan,Italy.

From November 1990 to November 1993.38 conrecutivc palienta(pts) with 1IlA and IIIB NSCLC entered an ongoing study of combined treatment with neoadjuvant MPV chemotherapy (CHT),surgery (S) and radiotherapy (RT). MPV regimen used as originalIy described b R.Gmlla - was: M fang/m2 d ,,29.7,. p lZOmg/mZ dl.29.7l.V 4m~/m2 d 1, Pmnh I d 8. 4.5mzlmZ d 15.22.29. then ever+ other week. CHT was ad&niatemd in day-hospital rcgim&. p witi prs a& post-hyd&tion and forred diuresis. dexametbasone 12.2hn8 I” ECOG-PS O-2: median age 4

wen before M. Main charsneristic. of the 38 p’s were: 7 yun(39.67); M 33.F 5: stage IIIA 23 (T3NO 5,T3NI

3.T3Nx I.TI-3N2 14). “IB 15 (T3N3 l.T4NO 3.T4Nx 4.T4NZ 7); histology: epidemmid 19, sdcnaea. 11: large cell ~a. 3, unclassified 5. We included T3NO.I pta because ,he pmznosb. even f better than in NOR sdvanad disease. is still unsatirfactorv: fuohennore pnmary CHT was adminirtered in the attempt to substitute lob&&y (L) for pne~mectomy (Pn). N+ was dirgnored by CT scan (ncdc. 22 cm) (33 p’s) or mcdlsstinosmpy (5 pts). Thirty-four pts am evalusble for toxicity and response, while 4 pU are sdII on CHT. We ahewed 3 crmplete maponsss (CR). 24 pnial nerponass (PR) (overall response 79.4%). 4 no change (NC) (11.8%) and 3 progerrivc disease (PD) (8.8%). There were 2 deaths secondary to reactivation of bncitary NbercoIo~i~ after CHT. Myelosupprrsrion was mild. Five pm experienced W 0 grade l-2 nephmtoxiaty I? and therefore stopped CHT after 1 (1 pt) or 2 (4 pb) P administrations. No p had major pulmonary vxicity andbmed to M. Acute emesis after P was commUed m two thirds of ps. Sane degree of alopecia, mild priphsnl neuropalhy and mild hearing loss were obscwed in most ps. IV19 Ill.4 ptr undewmt tbomcc,omy and 14 (73%) had cm,, Iclc resection of tie tumor. AU T3NO undewent L: 2 T3NI L and , pn: 1 ‘I?_NZ L; 2 T3 Is 2 L, 1 bilobecmmy and 2 Pn. As well, 5 pa with II18 disease undenuem rurg~al exploradon nnd 3 prs (20%) had ccmple,c rewcuc,, of the nmmr (2 pn, I L). No s”rSery ,eLated deaths occuned Two pts had no tumor m bi disease was obwwcd in aher 2 cases (lllA). 5

JY specimen (2 IlIB) and only micmscDpic wemy-five pls recavcd RT (5060 Gy) on

mediattinum and primary tumor ama, 3 stOpped RT for PD. 3 didn’t received RT for reaclivation of pulmonary Nbercdoria (2 pa) (x pax PS (1 p+ and 3 arc still ~1 radiation treatment. After Be planned treafmmt 160, @s were judged free of disease. With a median foUos-u of 24.5 mmthr (35-b). 20 pts (64.5%) are alive, 13 (42%) free of disease (8 IllA. P IlIB); 10 (32%) surviving more than 2 years. We conclude that MPV regimen is a hi& effective neoadjuvam treatment in stage Ill NSCLC, with an increased complete resection mte and less extended surgery in stage IllA. cccarionally chance of radical suugc and gmd rate of CR in stage IllB disease. In cur experience MPV is appliub,c in day- o~pttal regimen and RT is feasible after CHT x and S. Longer follow-up is heeded lo ewluate impact on survival of such combined UuLmc”t.

CONCOMITANT CEEI4ORADIATION TAERAPY IN STAGE III NON SMALL CELL CUNG CANCER. P.JUIN, J.F.POLLET,X. MURACCIOLE,J.P.ROCCASERRA,Y.ROLlAH, F.RIITANO,P.BERGERON.MARSEILLE.FRANCE

From february 1988 to january 1992, 31 patients with stage III non small cell lung carcinoma were treated by a concomitant chemoradiation therapy association :

Radiation therapy : 30 gy in three weeks and 15 fractions and, after a split of 3 weeks, 20 gy in two weeks and 10 fractions.

Chemotherapy : Carboplatin 40 mg/m2 x 3 each week of radiotherapy

Vindesine 2 mg first day of each radiotherapy's week.

There were 25 men and 6 women with mean age of 59 (range 40-74) all with good performance status, 11 stage III A and 20 stage III 8.

Toxicity was moderate with no grade III.IV hematological toxicity, and 1 grade III oesophageal toxicity.

All patients were evaluable for response. There were 8 complete responses (25,8 %), and 16 partial responses (51,6 %) for a 77,4 % objective responses rate.

12 patients (38,7 %) underwent surgery after this therapeutic approach.

Median survival was 20 months (4 to 48). Survival was significantly longer for patients with objective response.

129

DOSE FINOIWQ RADIoTENRwY (NSCLC).

STUDY OF eARmPLm1n (C) Am SIlnlITRlKoIJS (RT) IN STAGN III NON SfUU, CNLL LDNG CANCER

M. Wolf, C. G6rg, K. G&g, R. Pfab, K. Havemann. Dept. of Int. Med., Philipps-Univ. Marburg, Germany

In human lung cancer cell lines we were able to demonstrate radiosensitizing properties of C comparable to those of cisplatin. Therefore, a clinical trial was initiated to determine to maximum tolerated dose of C in Combination with RT in stage III NSCLC. RT was given at single doses of 2 Gyjday on days l-5 in weeks l-3 and 6-7. The total RT dose was 50 Gy. C was to be administered at escalating doses on day 1 in weeks l-3 and 6-7. Starting dose level of C was 100 mg/m*, following dose levels 120, 130, 140, 150, 160, 180. 200 and 220 mg/m*. Five patients (pts) were entered per dose level until intolerable toxicity (myelosuppreesion > WHO grade II) occurred in 315 pte. Fourty-five pts entered the protocol. The main characterieties were: 37 male, S female, median age 60 (37-75), median Karnofsky performance status SO % (70-100 *), stage III* 9 pts, stage III b 36 pts. Non hematologic side effects were rare. Dofe escalation of C was stopped at the level of 220 mgfm because of myelosuppression > WHO grade II in 315 pts. Response analyses showed 1 CR (2 a), 23 PR (51 %). 14 NC (31 $) and 7 PR (15 %). CR + PR was higher in pts receiving C doses of 150-220 mg/m* than in pts receiving the lower doses (60 % ve 47 a). Median survival was 11 months for all pts, 13 mo for pts receiving C doses of 150-220 mg/m* 100-140 mg/m*.

and 9 mo for pts receiving In conclusion, the maximum tolerated dose

of C in this setting was determined to be 200 mg/m* and response and survival analysis point to the suggestion of a dose-response relationsship of C as a radiosensitizer in NSCLC.

731

CONCURRENT HYPERFRACTIONATED IRRADIATION AND CHEMOTHERAPY FOR NON-SMALL CELL LUNG CANCER. PRELIMINARY REPORT OF A PHASE I/II RADIATION THERAPY ONCOLOGY GROUP (RTOG) TRIAL. RW Bvhardt*, CB Scott, DS Ettinger, WJ Curran, RLS Doggett, C Coughlin, C Scarantino, M Rotman, and B Emami. Medical College of WI*, Milwaukee WI, Am Co11 of Rad, Philadelphia PA, J Hopkins U, Baltimore Md, Fox Chase CC, Philadelphia PA, Radiation Oncology Ctr, Sacramento CA, Dartmouth College, Hanover NH, U Rochester, Rochester NY, SUNY, Brooklyn NY, Washington U, St. Louis, MO.

To define the toxicity and effectiveness of concurrent chemotherapy plus altered fractionation irradiation for non-small cell lung cancer (NSCLC), a phase I/II study was conducted of Vinblastine (5 mgJM2 weekly x 5 weeks) and Cisplatin (75 mg/M2 days 1, 29 & 50) given during twice daily irradiation (1.2 Gy, 6 hours apart) to 69.6 Gy in 58 fractions in 6 weeks. Eligible patients (42) had stage II (unresected) or IIIA-B NSCLC and KPS 2 70; 76% of patients had > 5% weight loss prior to study entry. All protocol treatment was completed in 58% of 33 reviewed patients. Acute toxicity was predominantly hematologic with 18/41 (44%) having 2 grade 4 and one septic death. There were 7/41 (17%) with 2 grade 3 esophagitis, two with grade 4 nausea and vomiting, one with 15% weight loss and one severe dehydration. In the early followup period, subacute hematologic toxicity 2 grade 3 persisted in 23/41 (56%) patients, with septic death in two patients on days 60 and 62. There were two grade 4 late lung toxicities. Complete response of primary tumor to protocol treatment was achieved in 21% and partial response in 24%. Median survival time was 12.1 months with an estimated one year survival of 51% (13 patients at risk) with 20 patients dead and 22 alive with followup.

Concurrent chemotherapy and hyperfractionated irradiation for NSCLC appears to be an intense regimen in terms of acute and subacute hematologic toxicity. Evaluation of late toxicity, local control and survival requires longer followup, but the regimen appears worthy of further refinement in ongoing and subsequent clinical trials.