176 Abstracts / Lung Cancer 14 (1996) 149-I 79

Pre-operative chemotherapy for stage IIla (NZ) non-small cell lung cancer Chella A. Luccht M, Ribechini A, Silvano G, Mussi A, Janni A et al. Departmentof ThoracicSugery. UniversityofPisa, Via Roma 67.56100 Piss. Eur J Surg Oncol 1995;21:393-7.

From June 1990 to December 1993,36 patients were enrolled in a phase 11 study, aimedat determining the feasibility of surgery, patterns of disease recurrence and survival after neoajuvant chemotherapy in non-small cell lung cancer (NSCLC) stage IIIA-N2. Twenty-seven patientsunderwent invasivestagingprocedures(i.e. mediastinoscopyor needle biopsy). Two CHT schedules were used. Cisplatin (P) 90 mg/mq, day 1, mitomycin (M) 6mg/mq,day 1,andvindesine (V)S mg/mq,days I, 8, 15, were administered every 3 weeks for 3 cycles in the tirst 20 patients. The last 16 patients were treated with cisplatin (P) 90 mg/mq. day 1, mitomycin (M) 6 mg/mq, day 1, and vinorelbina20 mgimq, days I, 8, IS. Thoracotomy was performed I S-20 days after haematological recovery inthe objective-responders. Thirty-two patients were evaluable for response to CHT. The overall objective response (OR) rate was 78.1%. There were three complete (CR) (9.4%)and22 partialresponses (PR) (68.7%). The 25 patients with OR underwent radical surgery (16 pneumonectomies, one bilobectomy. seven lobectomies and one wedge resection). The only morbidity reported was a late broncho-pleural ftstula (on post-operative day 37). There were three post-operative deaths in patients who underwent pnewnonectomy: two due to an empyema following a broncho-pleural in fistula and one by pulmonary embolism. Histology was negative for the three CRs Six patients with residual nodal involvement at surgery underwent radiotherapy. Relapse occurred in seven resected patients. Presently 14 patients are alive, all but one being disease-free. withamedian follow-upof30.5 months(l5- 47). Median survival was 31 months (5-47). Actuarial 3-year survival rate is 49%. Our results confirm the high response rate of CHT, as well asthe feasibility andthe overall low complicationrate ofboth treatments (CHT and surgery).

Bronchial artery infusion of chemotherapeutic agents plus external irradiation in the treatment of advanced lung cancer - A report of 37 cases Qian L-T, Cheng G-Y. Zhang H-Y. D~pawmettt ofRadiation (Incologv, Anhui Provirzcial Hospital, Hefei. Chin J Clin Oncol 1995;22:554-7.

Between February 1990 and December 1993, 37 patients with advanced lung cancer (stage 11133 cases, stage IV 4 cases) were treated with bronchial artery infusion chemotherapy (BAI) plus external radiotherapy (RT). Symptomatic relief was observed in 90.1% of patients, Remission rates (CR+PR) was 70.3% for those treated with BAI alone and 89.2% in pattents treated with BAl+RT. Follow-up for 4 to48monthsdemonstrated that 12 patientsin thisseriesare still living and 25 patients died, with a median survival period of 12 months. The overall 0.5-, I -, 2- and 3-year survival rates for all patients were 94.4%. 61.3%. 37.5% and 6.3% respectively. It is indicated that BAI plus RT, being safe and effective. is the treatment of choice for patients with unresectable lung carcinoma.

Adjuvant radiotherapy versus combined sequential che- motherapy followed by radiotherapy in the treatment of resected nonsmall cell lung carcinoma: A randomized trial of 267 patients Dautzenberg B. Chastang C. Arriagada R. Le Chevalier T, Belpomme D, Hurdebourcq M, Lebeau B, Fabre C, Charvolin P. et al. Service de Pneumologie. Groupe Hosp. Pitie-Salpetriere, 75651 Paris Cedex 13. Cancer 1995;76:779-86.

Background. The effect ofadjuvant chemotherapy after resection of nonsmall cell lung cancer (NSCLC) remains an unresolved question.

Methods. From October, 1982, to November, 1986, 267 patients with resected NSCLC were included in a randomized trial. The adjuvatn allocated treatments were either postoperative radiotherapy, 60 Gy in 6 weeks (radiotherapy group = 129 patients), or three courses of postoperative COPAC (cyclophosphamide, doxotubicin, cisplatin, vincristine, lomustine) chemotherapy followedbyasimilarradiotherapy schedule (chemotherapy/radiotherapy group = 138 patients). Rest&. The sex ratio (M:F) was 19/l; mean age was 57 f 9 years. According to postoperative staging, 8 patients were Stage I, 70 were Stage II, and 189 were Stage III. The histologic type was squamous cell carcinoma in 175 patients, adenocarcinoma in 57, and large cell carcinoma in 35. The minimum follow-up was 6 years. Four patients were lost to follow-up. Death was recorded in 233 patients. No significant difference was observed in terms of disease free interval (P = 0.47, log-rank test), or overall survival (P = 0.68, log-rank test). With respect tothe first site of relapse, distant metastasis occurred more tiequently in the radiotherapy group (P = 0.09, log- rank test) whereas local relapse occurred similarly in both groups (P = 0.27). An interaction was observed between lymph nodeinvolvementandtreantientintermsofoveraUsur+aJ. Conclusions. The CGPAC chemotherapy as postoperative treatment failed to improve overaBsurvival inpatientswithresectedNSCLCteceivingpostoperative radiotherapy but decreasedthepattemofmetastaticprogression,mainly in the N2 patients,

Results of various modalities of non-surgical treatment of small cell carcinoma of the lungs Kolek V, Gronych B, Zajic J, Vaclavik A, Cwiertka K. Kischova 3, 779 00 Olomouc. Stud Pneumol Phtiseol 1995;55: 173-8.

Authors evaluated results of treatment of small cell lung carcinoma. They analysed the results in relation to therapeutic schemes and to the extent of the disease. They examined 64 patients (59 male, 5 female, mean age 60 years). In 37 patients limited disease and in 27 patients extensive disease were present. In 3 1 % of cases they gave palliative therapy, in 14 % chemotherapy, in I1 % radiotherapy and in 20 % a combination of both methods. In 20 % of patients intensive therapy, consisting from a combination of chemotherapy, regional radiotherapy to the tumour, whole body irradiation and radiotherapy ofthe brain were applied. Survival in cases of limited disease was in average 8.2 months, in cases of extensive disease 4.3 months. Patients receiving only palliative treatment survived 2.2 months. Patients treated actively survived from 5 to 13.2 months. Patients treated with intensive therapy from the beginning of treatment had the longest survival.

Preliminary analysis of a phase II study of weekly paclitaxel and concurrent radiation therapy for locally advanced non- small cell lung cancer Choy H, Safran H. Department o/Radiation Therapy, Rhode Island Hospital, 593EddySt, Providence.RI02903. SeminQnCOl1995;22:Suppl 955-7.

Paclitaxel (Taxol; Bristol-Myers SquibbCompany, Princeton, NJ) is an attractive agent to combine with radiation for non-small cell lung cancer. WehavebeenconductingclinicaJtrialsofweeklypaclitaxelatid concurrent radiation therapy. In a phase I study in non-small cell lung cancer, we determined the maximum tolerated dose of paclitaxel to be 60 mg/m*/wk with radiation. Patients received paclitaxel60 mg/m’lwk as a 3-hour infusion for 6 weeks with radiation to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). From March 1994 to February 1995,33 patients have been entered by the Clinical Oncology Group of Rhode Island. The overall response rate (complete plus partial responses) of 25 evahtable patients as of March 1995 was84%,withaconfidence intervalof68to96.Themajortoxicity was esophagitis. Twenty percent of patients had grade 4 esophagitis. Only 8% of patients had grade 3 neutmpenia. Combined-modality

Abstracts /Lung Cancer 14 (1996) 149-179 111

therapy with paclitaxel andradiation is a promising treatment for locally concurrent thoracic radiation, withadegreeoftoxicitycomparable with advanced non-small cell lung cancer with a high response rate and that associated with other concurrent combined-modality regimens for acceptable toxicity. this disease.

CarboplatWetoposidelradiation plus escalating doses of paclitaxel in stage III non-small cell lung cancer: A prelimi- nary report Bonomi P, Faber LP, Recine D, Lincoln S. Rush University Medical Center. 1725 W Harrison St, Chicago, IL 60612. Semin Oncol 1995;22:Suppl9:42-7.

Large randomized studies have shown superior survival results for sequential chemoradiotherapy compared with radiation alone in stage III non-small cell lung cancer. Similarly, chemotherapy followed by surgery was associated with longer survival than surgery alone in small randomized trials. Despite these results, disease recurs in most stage III patients. To improve these results, we are studying escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combinedwithplatinumietoposideandsimultaneousthoracic irradiation as preoperative and curative therapy. Initially, paclitaxel was given at a starting dose of 35 mg/m2 intravenously (IV) over 24 hours on days I and 8; carboplatin (area under the concentration time curve) 4 mgimL ” min) IV was given on day 2 and etoposide 5 mg/d orally on days 1 to 5 and 8 to 12; cisplatin 50 mg/mz IV was given on day 23, and radiation 2 Gy was given on days I to 5 and 8 to 12. Courses were repeated every 28 days. Four of five patients treated at the second paclitaxel dose level (90 mg/m’) experienced grade 4 toxicity. The treatment regimen was changedtopaclitaxelgivenatastartingdoseof8Omg/mzIVover3 hours on day I, carboplatin (areaunder the concentration time curve4 mg/mL ‘. min) IV given immediately after paclitaxel, etoposide 40 mg/m* IV given over 1 hour on days 2 to 5, and radiation 2 Gy given on days I to 5 and 8 to 12. No grade 4 toxicity was observed in five patients treated at the first paclitaxel dose level (80 mg/m’). AAer two courses, pulmo- naryresection(lobectomyandpneumonectomy) wasperformed without fatalities in five patients. Although more data are needed, pulmonary resection appears feasible following treatment with this paclitaxel- containing regimen. Patient accrual is continuing to determine the maximum tolerated dose of paclitaxel.

Continuous carboplatin infusion during 6 weeks’ radiother- apy in locally inoperable non-small-cell lung cancer: A phase I and pharmacokinetic study Groen HJM, Van der Leest AHD. De Vries EGE, Uges DRA, Szabo BG. Mulder NH. Department oj”Pulmona~ Diseases. Universily Hospirul

Groningen. Oosfersingel 59. 9713 EZ Groningen. Br J Cancer 1995;72:992-7.

Concurrent paclitaxellcisplatin with thoracic radiation in patients with stage IIIA/B non-small cell carcinoma of the lung Antonia SJ, Wagner H, Williams C, Alberts M, Hubbell D, Robinson L et al. Division ofMedicul Oncolog.v, II. Lee Mofft Cancer Center. 12902Magnolia Dr. Tumpa. FL 33612-9497. SeminGncoll995;22:Suppl 9:34-7.

A phase I study was performed in 21 patients with previously untreated, locally inoperable, non-small-cell lung cancer(NSCLC) with ambulatory continuous carboplatin infusion together with continuous thoracic irradiation over 6 weeks. A dose range for carboplatin of I5 mg m-2 day-’ during the last 2 1 days (first level), during the last 3 1 days (second level), or during 6 weeks ofthe radiation period (third level) and thereafter 20 or 25 mg m-* day’ during 6 weeks ofradiation (fourth and fifth level) was used. The total radiation dose was 60 Gy given as 2 Gy day-’ for 5 days week-‘. The first three patients received radiotherapy without cru-boplatin. WHOgmdeIIVIVleucopeniaandthrombocytopenia occurred in the last two dose levels in two out of six and one out of six patients with 20 mg m.’ day’ respectively, and in all three patients with 25 mg m.* day’ (dose-limiting toxicity). One local infection around the portandasubclavianveintbrombosisoccurred. Radiationtoxicityofthe lung and oesophagus did not seem to be influenced by carboplatin treatment. Out of 21 patients one had a complete response (CR), ten partial response (PR), six stable disease (SD) and four progressive disease (PD). Total (TPt)and ultrafilterable plasma platinum (UPt) were measured in the last three dose levels withatomicabsorption spectrophote metry with Zeeman correction. The mean (s.d.) level for TPt for 6 weeks at 15,20and25mgm~‘day’was0.76(0.15),0.78(0.19)and0.90(0.22) mgl-~forUPt0.10(0.03),0.12(0.O2)and0.20(0.03)mgl-‘res~ctively. TPt concentration levelled off after 3 weeks. The mean (s.d.) CL(TB) for UPt was 28 1 i 2 I ml mir’ and correlated with glomerular tiltration rate (r = 0.61, P = 0.03). As estimated with the sigmoid E(max) model defined by the Hill equation the percentage reduction in platelets correlated withthe areaunderthe curve forUPt (r= 0.77).Themaximum tolerable dose of carboplatin with concomitant continuous 60 Gy radiotherapy is 25 mg m-* day’; the recommended dose for phase II or III studies is 20 mg rn-? day’ day for 6 weeks.

Reviews

Nine patients with stage IIIB non-small cell lung cancerwere entered into a phase II trial designed to determine the feasibility of giving a combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton,NJ)pluscisplatinconcurrentwiththoracicradiation. Pa&axe1 was given as a 24-hour infusion (135 mgim’) followed by cisplatin (75 mglm2) every 4 weeks, for a total of four cycles. Thoracic radiation was given concurrently with the first two cyclesofchemotherapy. fora total dose of 64.8 Gy over 6 weeks. Neutropenia and esophagitis were the most common toxicities, with 66% of patients experiencing grade 3 or 4 neutropenia and 55% experiencing grade 3 or 4 esophagitis. Grade 3 pulmonary toxicity developed in 33%ofpatients. All patients were able toreceive theFulldoseofradiation,althoughhalfofthepatientsrequired some modification of the chemotherapy regimen. There was one complete response and four partial responses, yielding a 56% overall response rate. This study demonstrates that it is feasible to treat patients with stage IIIB non-small cell lung cancer with paclitaxel/cisplatin plus

Accelerated induction therapy and resection for poor prognostic stage III non-small cell lung cancer Rice TW, Adelstein DJ, Koka A, TefA M, Kirby TJ, Van Kirk MA et al. Cleveland Clinic Foundation, Dept. of ThorocicKardiov. Surgev, 9500 EuclidAve. Cleveland, OH44195. AnnThorac Surg 1995;60:586- 92.

Background: Induction therapy and resection may improve the survival of patients with poor prognosis stage III non-small cell lung cancer, at the cost of significant treatment prolongation. The purpose of thisstudywastoassesstoxicity,response,andsurvivalofanaccelerated induction regimen and resection in poor prognosis stage III non-small cell lung cancer. Methods: Forty-hvo surgically staged patients with poor prognosis stage III non-small cell lung cancer received I 1 days of induction treatment consisting of96 hours of continuous chemotherapy infusions of cisplatin (20 mg .. m-* ” day*), 5 fluorouracil (I .OOO mg .’ m- * .. day2). and etoposide (75 mg ” rn.I ” day2) concurrent with accelerated fractionation radiation therapy (I .5 Gy twice a day, to a dose of27 Gy).