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usually given intravenously (I.V.)(7.5 g/m’/mts). Because of CNS toxicity, although rather mild in OIM therapy, it is suggested that the dose used I” schedule C should not be exceeded wlthin a fractional dose, 14 days treatment. More- over, the tumor response efficacy of OIM in NSCLC is com- parable to the rate achieved by IM given I.V. The total monthly 01 dose should not be less than the dose used in schedule B.

A PHASE II TRIAL OF PFL IN ADVANCED NSCLC

T.J. LYNCH, A.D. ELIAS. E. FREI, F.KASS, I. CLARK, A. DREYFUSS AND A. SKARIN. DANA-FARBER CANCER INSTITUTE AND HARVARD MEDICAL SCHOOL. 44 BINNEY S’IREET, BOSTON, MA 02114.

The combination of CDDP, S-FU and Leucovorin (PFL) has shown remarkable activity in squamous cell cancer of the head sod neck. Complete response rates in oar institution in advanced head and neck cancer approach 70 96. NSCLC also arises from the aerodigestive tract and its etiology is similarly influenced by environmental carcinogens. 30 patients with advanced ( 63 % stage IV. 37 W stage IIIB) NSCLC have been entered onto a phase II trial of PFL ( CDDP 25 me/m2 D l-5. Leucovorin 500 mglm2 D 1-6, and 5.FU 800 mp/m2 D 2-6 all given by continuous infusion). 80 % of pstienu had ECCKi performance status of O-I. 50 % of patients had adenocaxinoma and I7 % were squamous cell histology. Of the 30 patients entered, 20 patients are evaluable for toxicity and response. Response rates include 1 l/20 (55 46) partial responses, 8/20 (40 %) stable disease, and l/Z0 (5 %) progression. There were no radiographic complete responses. Mucositis was the most prominent toxicity with 61 96 having grade III/IV and 80 % of patients requiring a dose reduction of 5.FU/Ieucovorin for additional cycles. Hematologic toxicity included neutropenia in 33 % of patients and thrombocytopenia in 33 %. One patient died from sepsis m the setting of profound neutro~nia and mucosltis. Durability of response and overall survival data are being analyzed. We conclude that PFL is a promising regimen in the treatment of advanced NSCLC with a response rate in well selected patients in excess of 50 96. However this activity is gained at the cost of significant mucositis. Future trials will aon to reduce toxicity while preserving acuvity with the goal of using this regimen in the necadjuvaot setting.

REDUCTION IN THE INCIDENCE OFCHEMOTHERAPY-INDUCED FEBRILE NEUTROPENIA IN PATIENTS WITH SMALL CELL LUNG CANCER BY GRANULOCYTE COLONY STIMULATING FACTOR (r- metHuG-CSF). J. Crawford, D. Johnson, R. Staller. I. Tabbara. M. Kris, J. Glasdy, W. Gradishar. m. G. Lyman, A. Yahanda. R. Smith. M. Abeloff. V. Picozzi. M. Vincent. M. Stewart. and H. Ozer. St. Elizadeth’s Hospital of Boston and the G-CSF study group.

Patients with small cell lung cancer were enrolled in a multi-center, randomized, double-blind, placebo-controlled trial to assess the incidence, severity, and duration of febrile neutropenia following chemotherapy cyclophosphamide (day I). doxorubicin (day I), and etoposide (days l-3). Patients were randomized to receive single daily subcutaneous doses of placebo or r-metHuG-CSF (GCSF) beginning on day 4 and continuing through day 17 of a 21-day cycle, to be repeated for up to 6 cycles. Patients were removed from the double-blind study arm when the orimarv endooint. febrile neutrooenia [defined as an absolute neotr~phil cbont (ANt?) <1.000/mm3 ‘with a temperature >38.2”Cj developed. Patients then received open-label GCSF in subsequent cycles. At the time of this analysis, 126 patients had completed at least 1 cycle of chemotherapy that was available for anal&s.

At least one episode of febrile neutropenia was experienced by 75% of the patients in the placebo group verws 45% in the GCSF group (p <O.OOI). Of 50 patients who completed all 6 cycles of chemotherapy, 23 did not have an episode of febrile neutropenia: 3 patients on olacebo verses 20 patients on GCSF. In cycle I, the median’duration of Grade IV neutropenia (ANC <500/mm3) was 5.5 days for placebo verses 3.0 days for GCSF (p<O.OOl). For all cycles, the median days of Grade IV neutropenia was 5.0 days for the placebo group compared to 1.0 day for the GCSF group. However, once febrile neutropenia developed, the median durations of febrile neutropenia was 5 days for both treatment

groups; the median durations of intravenousantibiotics and hospital stays per event were also similar. However, due to the marked reduction in the event rate in the GCSF group, there was a 50% reduction in overall number of days of antibiotics and days of hospitalization during cycles with GCSF compared to placebo. The only consistently observed during clinical adverse event attributed to GCSF was mild to moderate bone pain, which was effectively treated with oral analgesics.

We conclude that the use of recombinant human granulocyte colony stimulating factor as an adjunct to chemotherapy in patients with small cell lung cancer was associated with minimal toxicity and clinically significant reductions in the incidence of febrile neutropenia; the incidence, duration, and severity of grade IV neutropenia; and the number of days of antibiotics and hospitalization.

Intensive Multimodality Therapy for Small Cell Lung Cancer (SCLC) Using Intensification with High Dose Chemotherapy and Autologous Bone Marrow Support. AD Elias. AT Skarin, T. Herman, M. Hunt, L. Ayash, C. Wheeler, G. Schwartz, I. Tepler, L Schnipper, Frei E Ill, K Antman.

While clear gains have been made with combination chemoradiotherapy in the treatment of SCLC, ultimately these responses tend to be short-lived with few long term survivors (2-3 years) 8 even rarer survival beyond 5 years. While dose intensity has contributed to complete response (CR), survival advantages have been elusive.

The unique feature of this trial is the combination alkylating agent with the use of intensive local radiotherapy. In this study, treatment consisted of: Induction chemotherapy to maximal response; Intensification with cyclophosphamide, cisplatin & BCNU (CPB) at 5625, 165, 480 mg/ms with autologous bone marrow support (ABMT); followed by chest radiotherapy (CTI) (50 Gy15 weeks) & prophylactic cranial radiation (30 Gy in 15 fractions). Involved field radiation was given for selected metastatic sites. Eligibility included histologically documented extensive (ED) or limited stage (LD) SCLC in CR or partial response (PR) to first line standard dose induction chemotherapy & a requirement of FVC & DLCO of 2 60% predicted at the time of intensification.

17 patients (pts) have been treated: 11 LD (4CR, 7PR prior to ABMT); 6 ED (lCR, 5PR prior to ABMT). Stage IIIA (Tl-3, N2) in 6; Stage IIIB (T2-4, N3) in 5; median metastatic disease sites 2 (l-7). Median age 45 years (25-61). Median induction cycles was 4 (2- 6). Two pts died (12%) of Candida infection. Decreased FVC & DLCO was observed in most pts & precluded CTI in 2.

Of IO evaluable pts, 6 converted from PR to CR. Two other ED pts had resolution of all soft tissue disease & bony sclerosis of residual bone scan abnormalities. Post ABMT, unmaintained median time to progression (TTP) & survival (S) were 10 & 16 months. Actuarial survival at 1 year was 64% & was 28% at 4 years with 3 pts (2LD, 1 ED) > 3 years. From initiation of induction chemotherapy, TTP & S for all pts were 15 & 20 months, Median S for LD & ED pts were 21 & 16 months, respectively. Of the 7 LD pts in or near CR, 6 remain DF (median followup of 12 months) and 1 developed adenosquamous lung carcinoma.

Relapse was almost exclusively in prior sites of involvement, All 3 pts who did not get CTI relapsed in the chest. Of 12 who got CTI, 3 relapsed in the radiation port. All 6 LD patients who remain disease free received CTI.

While the pts were carefully selected on the basis of physiologic function & performance status, disease parameters were skewed toward poorer induction response category & advanced disease at presentation. Despite this, the unmaintain remission and survival post ABMT and the overall survival from initiation of therapy is quite favorable compared to these statistics obtained from conventionally treated pts. Treatment of additional pts on this study with further followup is required. Ultimately, a randomized comparison between this approach and conventional chemoradiotherapy is needed to define the role of high dose chemotherapy with hematopoietic support in the treatment of SCLC.