3 months chemotherapy and thoracic radiotherapy for small cell lung cancer (SCLC)

161

before irradiation, and after 2 hours the medium was changed. Irradiation was given as a single dose in air. The effect on survival was recorded according to a growth retardation method, which was considered most suitable due to the low cloning efficiency of this cell line. The results demonstrate that bleomycin in a dose of 0.i resp 0.01 ug/ml together with irradiation in the dose level of 6 Gy and higher exerts a greater effect on survival than irradiation alone. Thus Bleomycin seems to cut off the very large shoulder in the dose survival diagram, that cha~ racterizes this cell line and makes repair of otherwise subletal damages impossible. However from our in vitro results it is hard to explain the surprisingly good effect found in the clinical study mentioned above, since we found no synergism i__nn vitro when only 2 Gy, used in the clinical study mentioned above, was administered. Further studies are needed to elucidate a possible synergistic effect also in the low dose range.

Ifosfamide, Mitomycin C and Radiotherapy in Non Small C~II Lung Cancer (NSCLC). Chetiyawardana , A.D., Cullen, M.H., Joshi ~, R.C., Stuart, N.S., Woodroffe, C.M. 1. Department of Radiotherapy and Oncology, Queen Elizabeth Hospital, Birmingham. 2. Manor Hospital, Walsall. Ifosfamide and Mitomycin C are 2 of the more active single agents in NSCLC. This study evaluates the 2 drugs in combination followed by local radiotherapy. Twenty-five ambulatory patients with inoperable non small cell lung ~ancer were treated with ifosfamide 5 g/m- as a 24 hour infusion with the concurrent administration of Mesna (160% of2the ifosfamide dose) and Mitomycin C 6 mg/m given as an intravenous bolus injection on the second day. The mean age is 59 years. All but one patient had squamous cell histology. Fifteen patients had limited stage disease and 9 had extensive disease. Twenty-three patients are assessable for response to chemotherapy: 8 achieving PR and one CR (verified bronchoscopically). The overall response rate is thus 39%. All but one response (a PR) were in LD patients. Seventeen patients including the 9 responders received thoracic irradiation (30 Gy in 8 fractions over l0 days) having completed chemotherapy. One PR was converted to a radiological CR. Fifty-five percent of all patients are alive at one year. There has been one death among the 9 responders (d 200) and 8 among 14 non-responders (d 48 - 294). All patients suffered chemotherapy induced alopecia but there were no treatment modifications due to my~losuppression, h~t~

morrhagic cystitis or other toxicity. Nausea and vomiting have been troublesome necessitating in-patient stay for 3-4 days. There has been one treatment related death. Ifosfamide and Mitomycin C is an active combination in limited stage squamous cell lung cancer. Combined Modality Treatment of Small-Cell Bronchial Carcinoma. Karrer, K. for the International Society of Chemotherapy (ISC)-SmalI-Cell Lung Cancer Study Group. Institute for Epidemiology of Neoplasms, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria. In 1979 a randomized cooperative trial was activated, comparing new sequential intermittent polychemotherapies (sq.CT) of 3 different alternating drug combinations given 12 x intermittently within 1 year after surgery with a chemotherapy (CT) of 1 combination of 4 drugs given 13 x intermittently within 3 years after surgery. Observations on 25 patients at 9 different cooperating surgical departments showed that sq.CT is applicable, no unexpected side effects occurred. The life table curves calculated per 1.7.1985 indicate the improvement of the survival rate 4 years after surgery for cure of patients receiving sq.CT compared with the survival rate of 31 patients receiving CT after surgery. Following the discussions at the 13th International Congress of Chemotherapy 1983 in Vienna, a new protocol was activated by a further enlarged cooperative ISC-SmalI-Cell Lung Cancer Study Group in October 1984. This protocol for a 2-arm randomized cooperative trial for patients operated for cure for pT.,_N_M_ • ~ 21.).U small-cell lung cancer is comparlng a comDlnea chemotherapy 1 as used in ongoing large cooperative trials in North-America and Europe with the sequential chemotherapy 2 as used before and described above. Results from the trial 1979-1984 and the ISC-trial are discussed in detail. 3 blonths Chemotherapy and Thoracic Radiotherap), For Small Cell Lung Cancer (SCLC). Carroll, K.B., Thatcher, N., Barber, P.V., Stout, R. CRC Dept. of Medical Oncology, Dept of Radiotherapy, Christie Hospital & Wythenshawe Hospital, Manchester, U.K. A short 3 month but intensive treatment regimen for SCLC was assessed in 70 patients. 55 patients had inoperable but limited stage disease, 15 other patients had contra-lateral neck nodes, pleural effusions and marrow involvement. 52% of the total patient group had elevated hepatic enzymes but no scan evidence of metastases. 3 courses at93 week intervals of Cyclophos- 9 phamide 2.5 g/m ", day 1 agd Etoposide 120 mg/mi.v. days 1 & 2, 240 mg/m- orally day 3 were given, followed by Methotrexate (MTX) i00 mg/m 2

162

on days 64 and 78. Thoracic XRT 4 MeV, 3250cGy, 8F, i0 days was started the day after the second MTX dose. No PBI was given. The response rate was 75% (54% CR), median survival ii months for all 70 patients and 16 months for CR. The patients who had bronchoscopically confirmed CR (26 patients) also survived significantly longer. No significant survival difference was observed between the 55 limited stage patients and the others. 37 patients are evaluable for relapse of whom only 5 have relapsed with the brain as the sole site. 7 patients died of probable infection associated with leucopenia, 24 patients had CT delayed by 1-2 weeks because of toxicity. 60 patients completed the planned treatment programme. The Karnofsky Performance score improved in the majority with treatment, KP > 80, 1 patient before treatment increased to 50 patients after treatment o The above short, 3 month CT+XRT regimen provides reasonable results comparable to those obtained with more prolonged treatment schedules. Integration of Hemibody Radiotherapy (RT), Combination Chemotherapy (CC), and Local RT (LRT) For Small Cell Lung Cancer (SCLC). Powell, B., Jackson, D., Scarantino, C., Pope, E., Choplin, R., Craig, J., Cruz, J., Richards, F., Muss, H., Case, D., McMahan, R., Spurt, C., White, D., Zekan, P., Stuart, J., Cooper, M.R., Capizzi, R. Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27103. Sequential upper and lower hemibody (UHB, LHB) RT (600 rad) has been used as a systemic agent in combination with conventional CC/LRT in 43 patients (~ts) with SCLC. Cyclophosp~amide (C-ig/m-), doxorubicin (A-50 mg/m-) and vincristine (V-2mg) were given weeks (wk) 0 and 3. UHB wk 6, CV wk 8 and LRT + whole brain RT 3 days later (200 rad x i0 doses) completed induction. Consolidation included C (750 mg/m ), A (40 mg/m ), V (2 rag) wk ii and 14, LHB wk 17, and CV wk 20. Maintenance CAV (c~nsolidation doses) was given wk 24 and q wk to a total of 24 months (mo). Response (complete (CR), partial (PR) and duration of response and survival are shown below by disease stage (limited (LD), extensive (ED)) . PCB (#)

LD(-'~) ED(20)

CR(15)

Relponse (Z) CR PR CR÷PR

~

8 3 -

&

-

Reeponee Durat ton (mo) Median(range)

S u r v i v a l (mo) Sedimn(ranRe)

2-~'~) 9 . 9 ( . 0 3 - 3 0 . 8 ) 14.O($.2-31.6') 7(35) $ . 8 ( 1 . 7 *12,0 ) 5.5(1.1-20.9~) 14.9(3.1 -30.8 +) >I6.~(6.4-31.6 )

Thrombocytopenia (26% of pts < ~0,000/mm 3) J and leukopenia (26% < 2,000 WBC/mm ) have been the major toxicities; 5 pts developed sepsis. Esophagitis was moderate in 13(28%)

severe in 2(4%) pts. Reversible radiation pneumonitis occurred in 1 pt. No drug related deaths occurred. It is possible to integrate sequential hemibody RT into a program of aggressive chemotherapy plus local RT with acceptable toxicity. The results at a median follow-up of 23 mo appear encouraging in limited disease; no benefit has been observed in extensive disease. Continuous Infusion VP-16, Bolus Cisplatin, and Simultaneous Radiation Therapy as Salvage Therapy in Small Cell Bronchogenic Carcinoma (SCBC). Rowland, K~., Bonomi, P., Taylor, S. IV, Maffey, S., Reddy, S., Lee, M.S. Rush Memorial College, Chicago, IL. Fifteen patients (pts) with SCBC failing previous combination chemotherapy were treated with continuous infusion VP-16 (60 mg/m-/ 24 hours for 96 hours), concomittant daily involved field radiation therapy (250 rads/da~, days 1-5), and IV bolus cisplatin (60 mgs/m day one) every 2-3 weeks. The starting doses of cisplatin and VP-16 were 30 mg/m in pts whose performance status (PS) was 3. Radiation therapy (RT) was given as a single daily fraction (i0 pts) or BID (5 pts) on days 1-5 for a maximum of 5 cycles (5000 fads). Patients characteristics included previous chemotherapy: CAr (ii pts), CCM (4 pts), and VP-16 (4 pts). Five pts failed 2 or more combination chemotherapy regimens. Median time from diagnosis to initi ation of VP-16-cisplatin and RT was 5.7 months. Ten pts had limited disease and 5 pts extensive disease at the time of study. Seven pts were PS 0-i and 8 pts were PS 2-3. RT was given for intra-thoracic disease in 14 pts and for hepatic metastases in one pt. Median number of cycles of RT and chemotherapy was 4. Six pts were continued on maintenance chemotherapy for 1-5 cycles (median 2). Eleven of 15 (73%) have responded (CR 6, PR 5). Eight pts who initially responded and subsequently failed had a median duration of response of 3 months. Sites of progression are: local only 3, distant only - 4, local and distant - I. One of three pts at postmortem exam were found to have no disease within the RT field. Actuarial median survivals since diagnosis and since start of salvage therapy for all pts is 16.8+ months and 5.7+ months respectively. Toxicity included: WBC < 2,000 (6 pts), platelets < 75,000 (3 pts), esophagitis (0 pts), BUN > 30 (0 pts), and creatinine > 2 mg/dl (0 pts). The regimen of continous infusion VP-16, bolus cisplatin, and concomittant radiation therapy produces clinical complete responses with acceptable toxicity in previously treated SCBC pts. Benefits of Radiotherapy (RT) in the Combined Modality Treatment of Small Cell Lung Cancer (SCLC). Bleher, E., Joss, R., Alberto, P., Kapanci, Y., Cavalli, F. for the Swiss Group for Clinical