Abstracts/Lung Cancer 12 (1995) 265-329

A prospective randomized trial to determine the benefit of surgical twectbn of midoal dkase following response of small cell lung cancer tocombmationckmotberapy Lad T, Piantadosi S, Thomas P, Payne D, Ruckdeschcl J, Giaeconc G. Medical Service, VA WestSideMedicalCente~ Chicago, IL. Chest 1994;106:SuppI:32OS- 23s.

Thra hundred hvcnty-eight patients with limited stage small cell lung eanccr were enrollcd in a trial to evaluate surgical trcatmcnt for such paticnts responding to chemotherapy. Cyclophosphamidc, doxorubicin, and vincristine wcrc administcrcd cvcty 2 I days for five cycles. Patients achieving at least partial response who had confirmation of pure small cell histologic fcatorcs by pathology review and who were fit enough for thoracotomy wcrc randomized to undergo or not to undergo pulmonary resection. All randomized patients received radiotherapy to the chest and brain. Two hundred seventeen (66%) of the patients aehicvcd objective rcsponsc (90 complete rcsponsc; 127 partial response). One hundred forty-six patients were random&d (66% of responders, 44% of all patients): 70 to surgery and 76 to no surgery. Results of surgery were 83% rcscction rate, 19% pathologic complete remission rate, and 9% with residual non-small ecll histologic features only, for a total of 28% eradication of small cell lung eanccr. The survival curves for the hvo arms are not different (log rank p=O.78). Median survivals wcrc I2 months for all enrolled patients and I6 months for those who were random&d. Actuarial 2-year survival is 20%. The results of this trial do not support the addition of pulmonary resection to the multimodality treatment of small ccl1 lung cancer.

Adjuvant cbemotkapy for non-small cell lung cancer Johnson DH. Division ojX4edical Oncologw Vanderbilt Unk School ofMedicine. NashviNe. TN Chest 1994;106:Suppl:313S-17s.

In the late 1970s and early 1980s. the Lung Cancer Shldy Group conducted a series of adjuvant chemotherapy trials in patients with resected non-small cell lung canecr Although sornc of these trials yielded modest survival benefit, the length of improved survival essentially equaled the time spent receiving chemotherapy. Consequently, few physicians routinely employ postoperative chemotherapy in spite of its thwretieal appeal. Possible explanations for the failure of adjuvant chemotherapy to provide meaningful prolongation of survival in non-small eelI lung canecr include lack of et&tivc chemotherapy. incorrect chemotherapy regimen, inadequate dose intensity, and possibly inadequate trial design. Futorc postopcrativc adjuvant trials should focus on treating patients with rcsccted early stage lesions (TINI, T2N1, T2NO). What role, ifany, newer antineoplastic agents will play in the postoperative settmg remains to be detcrmincd. Ncoadjuvant induction chemotherapy may well prove to bc a superior treatment strategy and deserves further investigation.

A ph~3 mdomized trial dimmediate eombiiatim chemotherapy vs dekyed combination cbematberapy in patienb with completely n?s&ed stage II and Ill non-small cell carcinoma oftbe lung Figlin RA, Piantodoai S. 200 UCLA Medical Plaza. Los Angeles, CA 90024. Chest l994;lO6Suppl:31OS-l2S.

The purpose of this trial (Lung Cancer Study Group LCSG] 853) was to perform a comparative study of immediate combination chemotherapy (cyclophosphamidc, doxorubicin, cisplatin [CAP]) vs delayed combination chcmothcrapy (CAP) administcrcd at the time of first systemic relapse in patients with completely resected stage II and stage III non-small cell Cancer of the lung. We randomly assigned I88 patients with resected stage II or stage III non-small eelI lung cancer of the lung (squamous, 53%; nonsquamous, 47%) to raeivc either immcdiatc or delayed combination chemotherapy. Careful intraopcrative staging was performed in all patients. Before randomization, patients were stratified according to stage-II (hilar nodes positive) vs UI (mcdiastinal nodes positive or T3)-and histologic features (squamous vs nonsquamous). Ninety four pattents were randomized to receive immediate CAP vs 94 patients randomized to receive delayed CAP Prognostic variables such as extent of discasc, histologic fcaturcs, sex, race, TN status, and Kamofsky performance status were equally distributed bchvccn randomized groups. The treatment groups differed with rcspcct to greater than 10% weight loss. Forty-one percent of patients had stage II diwasc and 59% of patients had stage IIl discasc. Median time to recurrence (I9 5 months) and survival (32.7 months) did not differ between treatment groups. Immediate combination chemotherapy was associated with a 12% reduction in risk of rccurrcnce and an 18% reduction in risk of death, although these rates wcrc not statistically significant. Histologic features. sex, race, Kamofsky performance status, nodal status, and weight change were associated with higher nsks of rccurrcncc.

Adjuvant chemotherapy with cyclopbosphamide, dororubicin, and cisplatin in patients with completely resected stage I non-small cell lung cancer: An LCSG trial Feld R, Rubinstcin I, Thomas PA. Princess Margarel Hosprfal, Toronto. Onf. Chest 1994;106:Suppl:307S-9s.

Objective: Two recent studies to resectable non-small cell lung cancer by the Lung Cancer Study Group (LCSG) suggested an advantage to adjuvant therapy with cyclophosphamidc, doxorubicin (Adriamycin), and cisplatin (CAP). Neither study had a no-treatment control amx The purpose of this study was to compare the CAP regimen with no treatment in patients with resectable early- stage non- small cell lung cancer. Mefhodr AAer complete resection, eligible patients wth TINI or T2NO non-small ccl1 lung cancer wcrc randomly assigned to receive or not to rcccive four cooms of CAP at 3-week intervals beginning on day 30 after surgery after stratification for histology, preoperative white blood cell count, and Kamofsky performance status before surgery. The CAP regimen consisted of 400 mglm’ of cyclophosphamide, 40 mp/m’ of doxorubicin, and 60 mpim’ of cisplatin. Of the 269 eligible patients entered in the study, IO1 had rccurrcncc and 127 had died at the time of analysis. The mean time since randomization is 6.4 years; mean follow-up is 3.8 years. There were no differences in time to recurrence or overall survival bchvccn the two groups even when analyses were adjusted for prognostic variables. Only 53% of the eligible patients received all four courses of CAP, and only 57% of such patients received all four cycles on time. Among the patients who had rccurrcnccs, 74% had their initial recurrence at a distant site. Conclusion: No survival bcnetit for CAP vs no- treatment control was found in this study. Therefore, adjuvant therapy with CAP should not be recommended for patients with resected early-stage non- small cell lung cancer Further trials to test adjuvant therapy arc indicated. but investigators should use better antlemetics to improve patient compliance as well as more active cisplatin- based chemotherapy regimens.

‘LbecompariswafCAPcharotber~pymdlPdiothernpyto radio-krapy alone for resected lung cancer with positive margin or in-volved highest sampled paratracheal node (stage IUA): LCSG 791 Lad T. h4edical Service, VA Wesf Side Medical Cenfer. Chicago. IL. Chest 1994;106:Suppl:302S-6S.

This study was conducted to determine the effect of adjuvant chemotherapy on locally advanced resected non-small cell lung cancer. Anatomic eligibility rcquircments were either positive rcscxtion margins or tumor involvement of the highest sampled mcdiastinal lymph node. One hundred seventy-two patients wcrc randomized to rcecive either postoperative thoracic irradratron alone or together with six cycles of CAP chemotherapy (cyclophosphamide, doxorubwn. and cisplatin). The chemotherapy arm showed significantly longer rceurrcncc- free surwal (p=O.O04). This benefit accrued to patients with both nonsquamous (p=O.Ol) and squamous (p=O.O8) cell carcinoma. At I year following randomization. there was a 14% difference m survival favoring the chemotherapy arm Chemotherapy significantly reduced distant mctastascs. Median sorvlval was 20 months for the chemotherapy arm and I3 months for the radiotherapy alone arm. The 2-year survival rate for the entire study population was 350,~. Toxic reactions were primarily predictable hematologic, GI, and alopecia toxicity expected from CAP Esophagitis was not a significant problem.

Effects of postoperative mediastinal radiation on completely resected stage If and stage Ill epidermoid cancer of the lung: LCSG 773 Weiscnburger TH. Deporbnenr ofRadiation Oncology Cancer Foundation of Santa Barbara, University of California. Los Angeles. CA. Chest 1994;106:Suppl:297S-301 S.

Among patients with lung cancer approximately 44% have disease limited to the chest. Patients with early lesions treated surgically have better survival rates than those with more advanced primary disease or nodal involvement. Postoperative irradiation should reduce local or regional recurrcncc and hopefully reduce systemic relapse

A placekoatrolled randomized double-blind study of adjuvant intra- pleural BCG in patients with resected TlNO, TlNl, or TZNO squamws cell carcinoma, adenocarcinoma, or large cell carcinoma of the lung: LCSG protocol 771 Gail MH. 6130 Executive Blvd. Rockville. MD 20852 Chest 1994;106: Suppl:287S92S.

This article reviews the design and findings of LCSG Protocol 77 I, a randomized double-blind comparison of postoperative adjuvant lntrapleural

Abstracts/Lung Cancer I2 (1995) 265-329

bacillus Calmctte-Guerin (BCG) against saline solution placebo control m 473 patients with rcs~cted TlNO, TINI, or T2NO non-small cell lung cancer. Patients were randomized from August 30, 1977, through October 20, 1980, and follow- up ended on Janualy I, 1990. There was no evidence of improved survival or time to recurrence among patients given BCG in contrast to earlier promising findings. A calculation suggests that false-positive results due to chance are not uncommon in small preliminary studies, indicating the need for larger confirmatory trials such as LCSG Protocol 771. Other contributions from this Protocol are also reviewed, including data on BCG toxicity, immunologic effects, patterns of recurrence. and identification of prognostic risk groups.

Gualdi GF, Mincrva RE, Volpe A, Polettini E, Anaveri G. Servicio TC-Rhf I Clinico Medico, Universita degli Studi ‘Lo Sopienra ‘, Roma Clin Ter 1994:145:313-7.

The above paper was intended to evaluate the usefulness of CT and MR in the study of radiation and chemotherapy induced pulmonary changes CT proved very useful in the evaluation of the remission rates of the tumor and of radiation- induced pulmonary effects and, hence to minimize its confusion with malignancies and other abnormalities. On the other hand, MR proved very useful in the differentiation behveen post-therapy fibrosis and recurrent tumor at least I3 months sfler chcmo-radiotherapy.

Clinical assessment of postoperative immuoocbemotherapy for mm- small cell lung cancer Ishii N, Miyamoto Y, Okada M, Tubota N, Yoshimura M, Ooyabu H et al. Deprrr~nen~ Of Surgery. Kobe Universiry School o/Medicine, Nada-kx, Kobe. Lung Cancer (Japan) 1994;34:883-9.

A study of postoperative adjuvant chemotherapy according to cell type and curability, either combined with or without immunotherapy using OK-432 wss cartied out in 138 patients with lung cancer who underwent resective surgery. Administration of OK-432 was selected by randomization. Of the total number of long c~ncc~ ULBCS. 123 patients were cvalublc. Five-year survival rates were 66.3% in OK-432 group (A), and 5 I .O% in control group (B), with no significant differences between the two groups. However, in patients who were curatively resected, the 5-year survival rate of the OK432 group were signiticantly better then that of the ccnWol group (group A, 70.9%, group B, 50.8%, p < 0.05), in particular in the edencarcinoma group and Stage I group (p < 0.05). Therefore, the postoperative administration of OK432 with chemotherapy contributed to improve the survival rate of curatively operated patients with lung cancer.

Daily low-dose cisplatin plus conatrmnt bighdose thoracic irradiation in locally advanced unfweetable oon-smakeil lung cancer: Results of apbaselISouthwest Oncology Gmupstudy Hszuka MB, Crowley JJ, Bonn PA Jr. O’Rourke M, Braun TJ, Livingston RB. Southwest Oncology Group. SWOG-8836, Operations O&e, I4980 Omicron DC San Anlonio, TX 78245-3217. J Clin Oncol 1994,12:1814-20.

Purpose: This single-arm phase II trial was designed to evaluate the efficacy and toxicity of continuous-course, highdosc thorn& irradiation (RT) combined with concurrent daily low-dose cisplatin followed by high-dose cisplatin consolidation in patients with locally advanced unresectablc non- small-cell lung cancer (NSCLC). The daily chemotherapy regimen was designed to optimize the radiosensitizing properties of cisplatin. Patienti and Methods: Sixty-five patients from 21 participating institutions were entered onto the study between April 1989 and May 1991. Protocol therapy consisted of daily intravenous (rv) cisplatin (5 mg/m’) plus concurrent continuous- course RT (61 Gy over 6% weeks) both delivered Monday through Friday each wak. After B 3- to 4-week rest period, this was followed by three 28day cycles of cisplatin at 100 m&n’ or subsequently 50 mglm’ administered IV on days I and 8 of each cycle. Results: Sixty-four patients were eligible; the majority had unresectablc stage IIIa (36%) or IIIb (55%) NSCLC. The remaining 9% had recurrent disease confined to the chest (five patients) or stage II disease (one patient). The feasibility of this regimen is demonstrated by the fact that only five patients (8%) were unable to complete daily cisplatin and RT because of toxicity Esophagitis (16%), leukopcnia (14%), nausea (S%), and vomiting (6%) were the most common scverc(gmdc 3) toxicities. There was only one life-threatening toxicity (g&c 4 nausea) and no treatment-

related deaths. The objective response rate was 39%. and six patients (9%) achieved a radiographic complete response (CR). The median survival duration for all patients was I4 months, and the I- and 2-year achtarial survival rates were 56% and 24%, respectively. For stage LUa patients, the median survival duration and 2-year survival rate were 17 months and 38%, as compared with 10 months end 14% for stage IIIb patients, respectively. Conclusion: Daily lowdose cisplatin plus concurrent high-dose cootinuous-course RT is a well-tolerated outpatient regimen. The survival results are encouraging and appear to be equivalent to more toxic combined approaches. These results warrant further testing of combined daily platinum analogs with RT.

Quality of life io patients with limited smakell carcinoma of tbe lung receiving chemotherapy with or without radiation therapy, for caocer sod leukemia group B Ahles TA, Silberfarb PM, Rundle AC, Holland JC, Komblith AB, Canellos GP et al. Center for Psycho-Oncology Research, Darbnouth-Hitchcock Medical Cente: One Medical Center Drive, Lebanon, NH 03756. Psychother Psychosom 1994;62:193-9.

Quality of life was assessed in 57 patients with limited small-cell carcinoma of the lung utilizing psychological scales that measured mood, functional status, and cognitive impairment. These patients received chemotherapy with or without radiotherapy to the primary tumor. All patients received prophylactic cranial radiation. Patients who received the combination of chemotherapy and radiotherapy to both the primary tumor and CNS had an increase in overall survival. However, because of the increased toxicity experienced by these patients, a decrease in quality of life was documented by measures of psychological distress when compared to patients receiving chemotherapy alone. The findings support the importance of utilizing quality of life measures in addition to measures of physical toxicity so that patients can make an infomred choice regarding treatment options.

Alternated appmacb with local irradiation and combination chemotherapy including cisplatin or carboplatio plus epirubicia sod etoposide in intermediate stage eon-small cell lung cancer Comclla P, Scopps G, Dspontc A, Musetta G, Ananie C, Maiorino A et al. Division of Medical Oncology A, Isto. Nazionale Studio Cura Tumori. via M Semmola. 80131 Nap&. Cancer 1994;74:1874-81.

Background: Prognosis of unresectable non-small cell lung cancer (NSCLC) patients is disappointing; their median survival time does not exceed 8-12 months. Recently, some authors reported an increased response rate and sometimes a prolonged survival for patients with intrathoracic disease treated with local irradiation combined with cytotoxic drugs. Methods: Fifty-eight consecutive patients with Stage IIIA or IIIB NSCLC were enrolled in a randomized Phase II trial of alternated treatment composed of four courses of combination chemotherapy and three cycles of local irradiation. Chemotherapy consisted of a randomly selected platinum compound (cisplatin [60 mp/m’] or carboplatin [300 mg/m’]) intravenously (i-v.) on Day I, cpirubicin (SO ms/m’) i v on Day 1. and etoposide (100 mglm’) i.v. on Days 1-3. A course of radlothcrapy consisted of 5 consecutive fractions (3 Gy per fraction, 1 fraction per day) for a total dosage of IS Gy per course. Each course of chemotherapy was alternated every 2 weeks with B course of irradiation so that the entire treatment was performed in I3 weeks Results: Of the S8 patients, 53 were evaluablc for response: 7 showed a complete clinical remission, end 25 reached a partial response, giving an overall response rate of 60% (95% confidence interval, 46%-74%). The tumors of four patients who showed a complete or partial response subsequently were surgically resected, and the complete disappearance of any residual tumor cells was documented histologically in hvo of them. No differera in response was observed behveen cisplatin- (I6 of 26 [62%]) and carboplatin-treated patients (16 of 27 [59%]), and no correlation was found behveen response and either stage or histology. Patients enrolled in the carboplatin arm experienced less severe leukopenia end vomiting than did those in the cisplstin Amy. Median freedom from progression and overall survival time were 28 and 39 weeks, respectively. Patients who responded had B significantly longer median duration of survival (49 weeks) as compared to non-responders (IS weeks). Conclusions: The alternated chcmoradiotherapy treatment obtained a high response rate with substantial toxicity. This approach did not seem to improve the pmgnosis of patients significantly. In this setting, the administration of carboplatin instead of cisplatin appeared to be tolerated better by the patients.