394

collateral flow drained into the azygos system. When it was obstructed, however. the collaterals drained into the inferior vena caval system. An importantcollateralpathway comprising the contraIatera1 brachioceph- alit vein and the jugular venous arch was also found, which has not previously been reported. Our diagrams of collateral circulation may provide a means of determining the site of obstruction in the superior vena caval system by RNSC.

Cardiac tampoaadeasanunasualpreseotationoflungraneer: Case report and review of the literature Huntsman WT. Brown ML, Albala DM. Depormenr of Surgery. Dartmouth-Hilchcock Medical Center, Hanover. NH 03756. Clin Cardiol 1991;14:529-32.

A case of cardiac tamponade as an unusual presentation of lung cancer and a review of the current literature are presented.

Surgery

Is there ever a role for salvage operations in limited small-cell lung cancer? Shepherd FA, Ginsberg R, Patterson GA, Feld R, Goss PE, Pearson FG, et al. Toronro General Hospiral, 200 Elizabeth SI., Toronfo, 0~. M5G 2C4. J Thorac Cardiovasc Sttrg 1991;101:196-200.

Combined modality treatment with chemotherapy and radiation produces tumor regression in most patients with small-cell lung cancer, but the impact on survival has been small, and less than 20% of patienrs with limited disease survive 2 years. Survival time is extremely short after failure to respond or relapse after treatment. Local control remains a problem, with one third of patients having recurrence only at the primary site. lnanattempt toprolong survivalandperhapsachievecure, we undertook surgical resection in 28 patients with limited small-cell lung cancer who did not have complete remission with standard treatment or who had only local recurrence after treatment. There were 28 patients, 22 male and six female, median age 61 years (range 41 to 76). All patients had been treated with chemotherapy and 13 had received preoperative radiotherapy to the primary site and medi- astinum. Eight patients underwent an operation for relapse after com- plete remission. Five patients had had no response to treatment, three had had a slight response followed by progression during chemother- apy, and 12 had achieved partial response but had greater than 3 cm residual masses. Twelve patients required pneumonectomy, IS lobec- tomy, one patient had unresectable disease, and two had bulky residual masses after the operation. Three others had microscopic residual disease. Pathologic examination showed only small-cell lung cancer in 18 patients, mixed small-cell and non-small-cell in four, and only non- small-cell lung cancer in six. There were only four patients with stage I disease, 10 with stage II, and 14 with stage III. The median survival from thedateofdiagnosis fortheentiregroup is 105 weeksandfrom the date of operation, 74 weeks. The projected 5.year survival rate is 23%. The two patients with residual masses died with local progression, and distant metastatic disease developed in 17 others. One patient died at 6 years without recurrent disease. Eight patients are alive 2 to 5 years after diagnosis. Seven of these patients required only a lobectomy, four had stage I disease, two had stage II, and two had stage III disease. Five had pure small-cell lung cancer and three had mixed small-cell and non- small-cell tumors. All of the patients with pathologic stage I disease remain alive compared with one of 10 with stage II disease and two of 14 with stage III. In summary, relapse or failure to respond to chemo- therapy may be due to non-small-cell lung cancer or a mixed tumor. A small number of patients with limited small-cell lung cancer without mediastinal node involvement may be cured by surgery after relapse or failure to respond to chemotherapy and radiotherapy.

Chemotherapy

a pharmacological strategy for circumvention of multidrag resis- tance in small cell lung cancer cell lines selected for resistance to doxorubicio Larsson R, Bergh J, Nygren P. Departmm ofClinicalPhnrmocology, Universiry Hospital, Uppsala University, S-751 85 Uppsala. Anti- cancer Res 1991;11:455-9.

The small cell lung cancer (SCLC) cell lines U-1285 and U-1690 were adapted to growth in continuous presence of doxombicin (Dox). The resulting cell lines U-1285R and U-1690R were investigated with respect to sensitivity to the glutathione (GSH) depleting agent buthion- ine sulfoximine (BSO) and the immunosuppressant cyclosporin A (CsA) as well as the Dox resistance modifying ability of these agents. The parental U-1285 cells were more sensitive to BSO compared to parental U-1690 and the multidrug resistant (MDR) sublines, whereas no difference in sensitivity to CsA was observed between parental and MDR lines. BSO (10 pM)orCsA (1 &ml) alone wereable to partially reverse Dox resistance in the MDR cell lines, CsA being only margin- ally active in U-1285R cells. However, the combination of these two drugs at the same concentrations completely reversed Dox resistance in the MDR U- 169OR cells whereas the combination was less effective in the U-1285R cells. The results demonstrate that a combination of low concentrations of BSO and CsA, only partially active by themselves in modifying Dox resistance, may be used as a pharmacological strategy to increase Dox sensitivity in wme MDR SCLC cells.

Neoadjuvaat chemotherapy of non-small cell carcinomas Pujol JL, Michel FB. Clinique des Maladies Respirafoires. Hopital 1’Aiguelongue. Rue du Major Flandre, F 34059 Monfpellier Cede*. F’resse Med 1991;20:418-22.

Lung cancer is frequent and serious. Squamous cell carcinomas, adenocarcinomas and undifferentiated non-small cell carcinomas ac- count for 80 percent of all lung cancers. Patients with one or the other of these carcinomas at the localized stage may benefit from complete and potentially curative surgical resection, but they represent only one quarter of all carcinomas. In patients with regionally more advanced carcinomas, notably when the mediastinal lymph nodes are invaded, sttrgicalresectiononly resultsina5 to 15 percentsuwival rateat S years. At this stage of lung cancer, an effective cytostatic treatment may impmve the survival rate, inasmuch as most therapeutic failures are due to metastatic progression. Neoadjuvant (preoperative) chemotherapy is now undergoing evaluation by controlled trials. This therapeutic suat- egy rests on two arguments: 1) patients treated with chemotherapy for locally advanced lung carcinomas may subsequently benefit from complete resection in over 50 percent of the cases: 2) neoadjuvant chemotherapy might sterilize the subclinical metastatic disease at the time of diagnosis. Studies are in progress to evaluate the effectiveness ofneoadjuvantchemotherapyin termsofsurvival.LJntilthefinalresults are available, this treatment cannot be proposed as a consensual therapeutic solution, but feasibility studies are encouraging.

Combination chemotherapy and interferon aZb in the treatment of advanced non-small-cell lung cancer Ardizzoni A,RossoR, SalvatiF,ScagliottiG, SoresiE,FemuaG.etal. Medical Oncology Deporfment, Isrituto narionale per la ricerca Su[ cancro, Viale Benedeffo XV, 10, 16132 Geneva. Am J Clin Oncol Cancer Clin Trials 1991;14:120-3.

Thirty-four patienrs with previously untreated advanced non-small- cell lung cancer were treated with a combination of polychemotherapy and recombinant interferon. Chemotherapy consisted of CYC~O-

395

phosphamide, 400 mg/m”, epidoxorobicin, 50 mg/m2, and cisplatin, 40

mg/m’ (CAP) i.v. on day 4; recombinant a2b interferon (ra2b IFN) was given i.m. daily at the dose of 3-5 MU from days 1 to 7. The treatment was repeated every 4 weeks. In the 32 eligible patients the overall response rate was 19.3% (95% C.L. 7.4-37.4%). Non-hematologlc toxicity consisted formerly in flulike symptoms and fatigue complained of by37.5% and 31.2%ofpatients,respectively,and vomiting reported in 68.7% ofpatients; grade III-IV myelotoxicity was observed in 12.5% of cases. In no case was the toxicity life threatening. The median overall actuarial survival and progression-free survival were 37 and 20 weeks, respectively. This study indicates that the combination of CAP chemo- therapy and raIFN is feasible and active in the treatment of advanced non-small-cell long cancer.

Differentialgrowthinhibitionandenhanccmentofmajor histocom-

patibility complex class I antigen expression by interferons in a small-cell lung cancer cell line and its doxorubicin-selected mul-

tidrug-resistant variant Cole SPC, Campigotto BMT, Johnson JG. Elliott BE. Borferel! Hall, Cancer Research L.aboratories, Queen’s Unrversiiy, Kingston. Oni.

K7L 3N6. Cancer Immunol Immunother 1991;33:274-7. Expression of class I and class II major histocompatibility complex

antigens on a human small-cell lung cancer cell line and its multidrug- resistant variant was examined before and after exposure to interferon a(IFNa) and IFNgamma by flow cytometry. Neither IFNIX nor IFN- gamma induced class II antigen expression on tbe drug-sensittve or resistant cell line. Induction of class I antigen expression along with an inhibition of proliferation was observed in both cell lines after IFNa treatment. On the other hand, IFNgamma treatment resulted in growth inhibltionandenhancementofclassIantigenexpressioninthesensitive cell line but not the resistant cell line. The differential response of the two cell lines to IFNgamma cannot be directly attributed to the acqw sition of drug resistance but it suggests that further investigation of the possibility that drug-sensitive and resistant small-cell lung tumors may respond differently to immunotherapies that include IFNgamma is warranted.

A phase II study of navelbine (vinorelbine) in the treatment of non- small-cell lung cancer

Depierre A, Lemarie E, Dabouis G, Gamier G, Jacoulet P. Dalphm JC. CHRIHopirol St. Jacques 2, place Sad-Jacques, 25030 Besancon Cedex. Am J Clin Oncol Cancer Clin Trials 1991: 14: 115-9.

Navelbine (vinorelbine, NVB) is the tirst semisynthetic 5’-nor-vinca- alkaloid selected for clinical trial. NVB has been shown to have a good level of activity against different experimental solid tumors m ammals, with low neurotoxicity. In the phase II study, 78 patients with an inoperable non-small-cell lung cancer (NSCLC) were treated with NVB at a weekly dose of 30 mg/m’. No pattent had previously received chemotherapy. Twenty-threeofthe78eligiblepatients showedapartial response (29.4% with a 95% confidence limits: 19.5-39.5). Eight patients were not evaluable and Ihe percentage of partial response were 32.8% in the evaluable patients group. The median response duration was 34 weeks. and the median survival time for the overall population reached 33 weeks. Grade 3-4 leukopenia was seen in 12.5% of cycles. No thrombocytopenia occurred. At the dosage schedule used, NVB seems a very promising agent in the treatment of NSCLC.

Phase II trial of amonafide in patients with stage III and IV non-

small-cell lung cancer

Berger MZ. Kris MG, Gralla RJ, Marks LD, Potanovrch LM, Dimaggio JJ, et al. MemorialSloan-Ketfering Cancer Center. 1275 York Avenue,

NewYork.NY1C4J21.AmJClinOncolCancerClinTnals 1991:14:124- 6.

Amonafide (benzisoquinolinedione, nafidimide. NSC 308847) is an anticancer agent that functions as a DNA intercalator. Sixteen patients with stage III or IV non-small-cell lung cancer who had not previously received chemotherapy were given amonafide at an initial dose of 300

mg/m’i.v.daily for5 daysevery 21 days. NomajorobJectlveresponsea were observed among the 14 patients adequately ueated (95% confi- dence limits O-20%). Local reactions at the injection site or phlebitis were seen in 14 of the 16 patients. Leukopenia (44%), nausea or vomiting (38%), and thrombocytopenia and rash (each 25%) were also noted. With the low response rate and the toxicity observed, amonafide at this dosage and schedule has limited use in the treatment of non- small-cell lung cancer.

Etoposide and mitomycin in the treatment of non-small-cell lung

cancer. A phase I-II evaluation EttingerDS,BitranJD,ComisRL,LangerCJ,HanvoodKV,H~isCL, et al. Johns t!opkins Oncology Cenrer, 600 North Wolfe Sweet. Bat&

more.MD21205. Am JClinOncol Cancer ClinTtials 1991;14:127-32. Sixty-five patients (20 patients who had had prior radiotherapy and

45 patients who had not had prior radiotherapy) were entered into a study evaluating escalating doses of etoposide and mitomycin in the treatmentofnon-small-cell lungcancer(NSCLC).Twenty-twopercent of patients who had not received pnor radiotherapy responded to the chemotherapy, compared with 5% of patients who had received prior radiotherapy. The best response rate and median survival time was 30% and 31.9 weeks, respectively, seen in three of 10 patients receiving mitomycin 10 mg/M2 i.v. day 1 and etoposide 100 mg/M’ I.V. days l-3. The major toxicity was hematologic - mainly leukopenia, in 59% of patients who had had no prior radiauon therapy and were receiving mitomycin 10 mg/M2 i.v. day 1 and etoposide 150 m&l2 i.v. days l-3 (grade 3 and 4 hematologic toxicity). The mitomycin-etopostde drug combination has some activity in patients with NSCLC who have not recetved prior radiotherapy. The recommended starting dose 1s mtto- mycin 10 mg/M2 i.v. day 1 and etoposide 100 mgiM* i.v. days l-3, administered every 4 weeks.

Adjuvant chemotherapy for Tl-ZNOMO small cell lung cancer:

Single-agent or combination chemotherapy? Macchiarini P, Hardin M, Basolo F, Bruno J, Angeletti CA. Service of

Thoracic Surgery, Universiry of Piss. Via Rome 67, I-56100 Piso. Cancer Invest 1991;9:19-25.

In an attempt to address the schedule of adjuvant chemotherapy in surgically resected Tl or T2NOMO small cell lung cancer, 12 patients were randomized to receive 6 courses of either single-agent (high-dose epirubicin) or combination (cyclophosphamide, epirubicin, and eto- poside) chemotherapy, at 3-week mtm-vals. No tboracic radiotherapy was admmistered while prophylactic cranial irradiation (30 Gy/lO fractionsl:! weeks) was given. With a 25.month median followup, overall estimated 2-year and median survival were 83% and 26.5 months (range 16-34+), respectively. Ten pat&o are currently ahve and disease free. No significant difference in 2.year survival was observed between the two adjuvant treatment modalmes and median survwal was 28 months (range 13.34+) for combmation and 21 months (range 14.29+) for single-agent chemotherapy. Although at high doses. epirubicin resulted in a moderate clinical and histological cardiotoxic- ity and a remarkably reduced incidence of severe (WHO grades 3 and 4) treatment-related morbidity compared with the combination regi- men. These prelimmary results suggest that comparable survival and reduced toxicity might be expected with an active smgle-agcnl as adjuvant chemotherapy in TI or T2NOMO small cell lung cancer.

The effect of lonidamine alone and in combination with cisplatin on in vitro growth and viability of lung squamous cell carcinoma cell lines Raaphorst GP, Ko D, Fe&y MM, Danjoux CE, Maroon J. Evans WK. Omzwo Regional Cancer Cenrre, 190 Melrose Avenue. Ormva. Onr

KIY 4K7. Anticancer Res 1991;11:41-7. Two non small cell lung cancer (NSCLC) cell lmes were tested in

vitro to evaluate tbe effect of lonldamine, cisplatin and combmations of these rwoagents using different doses and schedules. Lonidamine alone at concenvatlonsgreater than 50 pg/ml caused inhibition ofcell growth