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).

178 Abstracts / Lung Cancer 14 ( I996) 149- I79

Induction was followed in 4 weeks by resection. postoperatively. a second course of continuous chemotherapy and concurrent accelerated fractionation radiation therapy (postoperative dose 13 to 36 Gy) was given. Results: Despite some degree of induction toxicity in all patients there was only one induction death (2.4%). A clinical partial response was seen in 24 patients (57%). Thirty-six patients (86%) underwent thoracotomy, and resection was possible in 33 (79%). Pathologic downstaging was seen in 17 patients (40%). and 2 patients (5%) had no residual carcinoma at operation. There were I1 postoperative complications(3 I%)and4postoperativedeaths (I 1%). Thirteen patients (3 1%) are alive and disease-free, 24 (57%) have persistent disease or haverecurred (ISdistant, 5 locoregional.4 both),and9patientsare alive with disease. Tbe median survival is 2 1 months and the 2-year Kaplan- Meier survival is 43%, with no differences identified between stages IIIA and IIIB patients @ = 0.63). Conclusions: We conclude that accelerated induction therapy and resection in poor prognosis stage III nonsmall cell lung cancer (I) is toxic, with a 12% treatment mortality; (2)iseffectivewitha79%resectionrateand40%pathologicdownstaging rate; (3) provides excellent local control; (4) may prolong survival; and (5) is of value in stage IIIB as well as stage IRA patients.

Other treatment modalities

Radioimmunotherapy of small-cell lung cancer xenografts using “‘I-labelled anti-NCAM monoclonal antibody 123C3 Kwa HB, Verhoeven AHM, Storm J, Van Zandwijk N, Mooi WJ, Hilkens J. Department of Tumour Biolog.v. The Netherlands Cancer Insrirute, Plesmanlaan 121. 1066 CX Amsterdam. Cancer Immunol Immunother. 1995;41: 169-74.

We have studied the therapeutic efficacy of ‘3’I-labelled monoclonal antibody 323C3 in human small-cell lung carcinoma xenografts established from the NCLH69 cell line in nude mice. Several radiation doses were administered intraperitoneally and different treatment schedules were tested. The maximal tolerated dose, 2 x 500 Ci, resulted incompleteremissionoftumourssmallerthan200mm’and long-lasting remission (more than 135 days) of the larger tumours. In control experiments, treatment with unIabelledmonoclonal antibody 123C3 did not affect the tumour growth rate, while the effect ofradiolabelled non- relevant, isotype-matched, monoclonal antibody M6/1 was minor and transient. Regrowth of the tumours occurred in ah cases and could not be attributed to loss of neural cell adhesion molecule (NCAM) expres- sion. Tumour recurrence is probably caused by insufficient radiation dosage. Radiation-induced toxicity was monitored by assessment of weight and bone marrow examination. Weight loss was observed in all treatment groups, but the mice regained their initial weight within 14 days, except for the group receiving the highest radiation dose (3 x 600 Ci). In thts group all mice died as a result of radiotoxicity. Of the mice injected with 600 Ci radiolabelled control antibody, 50% died within 2 weeks after administration. Apparently the higher uptake of the radiolabelled monoclonal antibody in the tumour reduced systemic radiation toxicity.

Nd YAG laser and brachytherapy in the treatment of lung cancer Mare1 M, Stastny B, Fiser F, Kubecova M, Skacel Z, Trefny M. Pneumologicka Klinika. I Lekarska Fakulta, Univerzita Karlova. Veleslavinska 1. 162 00 Praha 6. Stud Pneumol Phtiseol 1995;55: 165- 72.

Authors present their first 2-year experiences with the Nd YAG laser therapy in 65 patients with lung carcinoma. They applied laser using bronchoscopy, mostly in general anaesthesia. In cooperation with

radiotherapeutists I6 of them received also brachytherapy. The treated group consists of 56 male (mean age 59 years) and 9 female (mean age 66 years). 70 % of patients obtained also external actinotherapy in addition to laser- and brachytherapy. The mean interval between the diagnostics and the first application of laser was 8 months (median 2 months). Authors treated with laser mostly endobronchial lesions in the left main bronchus (37 %). They achieved subjective improvement in 63 %, hemoptysis decreased in 33 %; worsening occurred in4 %. The most frequent complication of laser therapy was haemorrhage in 9.2 % of cases. Up to the date of evaluation 59 patients died, 6 were still alive. The time from the diagnostics up to death was 17 months (median 11). since the first laser therapy to death passed in average 7 months (median 4). Six patients lived since the diagnostics in average 17 months, from the first laser therapy 15 months. 15 patients treated with combined laser- andbrachytherapy, survived in average 8 months (median 8) since the first laser therapy session. 44 patients treated with laser and other methods than brachytherapy died in average 8 months (median 3) after first laser therapy. Authors conclude from this experiences that both methods are suitable for palliative treatment of lung carcinoma with endobronchial propagation.

Bronchioloalveolar carcinoma HsuC-P,ChenC-Y, HsuN-Y. DivisionofThoracicSurgety, Departmenl ofS~rrgery, Taichung Veterans General Hospital. 160. Set 3. Taichung- Kang Rd., Taichung. J Tborac Cardiovasc Surg 1995; 110:374-g 1.

Bronchioloalveolarcarcinomaisasubtypeofadenocarcinomaofthe lung with a relatively better prognosis. We reviewed the cases of 50 consecutive patients with bronchioloalveolar carcinoma treated during a I O-year period and attempted to analyze factors related to prognosis. During the IO-year study period, the prevalence of bronchioloalveolar carcinomarelative toadenocarcinomaofthe hmgremainedsteady. The subjects included32 maleand 18female patientswithmeanagesof64.7 years and 55.1 years. respectively (p = 0.0030). The preoperative radiographic findings included 40 cases of localized and 10 cases of diffuse bronchioloalveolar carcinoma. The clinicopathologic TNM staging included 20 patrents with stage I cancer, 4 with stage II cancer, I I with stage IIIa cancer, 3 with stage IIIb cancer, and I2 with stage IV cancer. Forty patients with clinical stage I, II, or III disease underwent operation (operability 80%). The resectability rate was 90% (36 of40). Thirty-four procedures were considered as curative. The overall cumulative survival at 5 years was 22.2% (46.4% for stage I). Different TNM stages showed significant differences in survival time (p = 0.000 I J. The median survival times were 64.6 months for stage I48.0 months for stage II, 24.7 months for stage IIIa, 9.0 months for stage IIIb, and 4.5 months for stage IV disease. The median survival time for localized bronchioloalveolar carcinoma was 27.5 months, and the median survival time for diffuse bronchioloalveolar carcinoma was 4.3 months@= 0.0002). Themediansurvivaltime forthecurativeresection group was30.6months,andthemediansurvivaltime forthe noncurative resection or nonresection group was 5.8 months (p = 0.0001). On the basis of this study we conclude that (I) the prevalence of bronchioloalveolar carcinoma is quite steady, (2) bronchioloalveolar carcinoma presents at an earlier age in women, (3) bronchioloalveolar carcinoma frequently presents with lymphatic spread or systemic metastasis at diagnosis, (4) most localized bronchioloalveolar car- cinomas are resectable and the prognosis with this type is better than that of the diffuse type, and (5) long-term survival correlates closely with initial roentgenographic appearance. TNM stage, and completeness of surgical resection.