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Lung abstract ASCO 1999

ASCO abstracts (99 – Lung, 00 – 2 NHL)
ICORG is very proud to announce that the 97-03 lung study was chosen to be presented in poster format at ASCO 1999 in Atlanta, this is a considerable achievement in view of the fact that less than 100 abstracts were chosen out of a total of more than 600 submissions.

Please see the text of the abstract below:

97-03 LUNG STUDY

Phase I/II evaluation of escalating dose Docetaxel (Taxotere, T), Ifosfamide (I) and Cisplatin (C) with Lenograstim (L) support, in patients with Stage III/IV Non Small Cell Lung Cancer (NSCLCa): An Irish Clinical Oncology Research Group (ICORG) study.

J Crown, P Donnellan, C O'Sullivan, S Rowan, M Jones, KM Chan, K Duffy, M O'Leary, O Breathnach, B Moulton, D MacErlean, M Schrance, R Murray, S Nutty, C Flynn, D Fennelly, M Moriarty, S O'Neill, V Lynch, W Mc Nicholas, C Gallagher, J Armstrong. St. Vincent's University, St. Luke's & Beaumont Hospitals, RPR Ireland, & ICORG Central Office, SVUH, Dublin, Ireland.

Three drug P-containing regimens have been reported to produce objective responses (OR) in 30 – 60% of patients (pts) with NSCLCa. More recently T has been reported to produce OR in 20 – 35% of pts with NSCLCa. The dose limiting toxicity (DLT) of T+C is neutropenia and gastrointestinal (GI). Pts/methods: We performed a phase I/II study of escalating dose T/I/C (dose escalation schedule in mg/m2: Dose Level I(3pts) 60/1500/75; II(4pts) 75/1500/75; III(3pts) 75/3000/75; IV(2pts) 100/3000/75) with L support (33 IU sc,days 3-10). 16 additional pts were treated at L III, as phase II. Patients with stage III disease received four cycles + radiation; stage IV six cycles. Treatment was in-patient. Pts received Mesna + aggressive hydration. Results 28 pts were treated (12 phase I, 16 phase II; 9 females, 19 males; 17 stage III, 11 stage IV). Median (med) age was 58 (range 37 – 69). Med Karnofsky performance status was 90 (range 70 – 100). Med cycles of treatment 4 (range 1 – 6). Maximum tolerated dose (MTD) of T/I/C was 75/3000/75. Grade III diarrhoea and nausea was DLT at Level IV. Adverse events necessitated admission in 15/116 cycles (5/50 cycles phase I, 10/66 cycles phase II), including 6 for GI toxicity and 1 each for febrile neutropenia (FN), renal, pulmonary embolus, atrial fibrillation, anaemia, infection, cardiac, morphine withdrawal and progressive cancer. While grade IV neutropenia was seen in 26/116 cycles (1 level I; 3 level II; 3 level III; 19 phase II), there was only one episode of FN. Dose reductions were required in 13/116 cycles – 8/50 phase I (7 GI, 1 renal toxicity), 5/66 phase II (4 renal, 1 GI toxicity). Grade II neuro-sensory toxicity and grade III fatigue were reported in 3 and 7 pts respectively. 3 pts were inevaluable for response (too early-2, early withdrawal-1). The OR rate for remaining 25 pts was 60% (stage III-62.5%, stage IV-55.5%). At MTD (phase I+II) OR was 58.8%. Med duration of response is 7months (m), (range 3-28m). With med follow up of 16m, 12/25 are alive, 8 are progression-free (3-28m; med 8m).

Conclusion: TIC 75/3000/75+L support is well tolerated, and appears to be a highly active regimen in NSCLCa. Phase III trial is planned.

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For ASCO 2000 in New Orleans two submissions have been made, the 97-04 NHL and the 97-05 NHL protocols.

Please see the text of these two abstracts as submitted below:

97-04 NHL STUDY

Feasibility and Activity of a Filgrastim(G)-Supported Non-Autograft Requiring Accelerated Multi-Cycle High-Dose Chemotherapy Regimen for Advanced Aggressive non-Hodgkin’s Lymphoma(NHL): An Irish Clinical Oncology Research Group Study

J Crown, P Donnellan, M. O'Leary, KM Chan, C Gainford, J Ballot, T King, B Moulton, D McCarthy, D Fennelly. Departments of Medical Oncology/ Haematology, St. Vincent's Hospitals, Dublin 4, Ireland (Supported by AMGEN).

Although aggressive NHL is a highly chemotherapy-sensitive neoplasm, only 50% of patients (pts) are cured. High-dose chemotherapy with progenitor (PBP) autografting has been shown to be superior to conventional therapy for relapsed disease, and is also gaining acceptance in the primary treatment of high-risk NHL. There is a risk of re-infusion of cancer cells with autografting. Cyclophosphamide (Cyc) and etoposide (VP-16), can be delivered in very high doses without PBP's, using G as support. We devised an accelerated multi-cycle high-dose regimen with G as sole haematopoietic support.

Regimen: Doxorubicin(A) 80 mg/m2 days(d) 1, 15, 29; Vincristine 2mg d 1,8,15,22,29,36, Dexamethasone(40mg) on d 1-5, 15-19, 29-32; VP-16 1500mg/m2 in divided doses over d 43-45; Cyc 5.0gm/m2 in divided doses d 57-58 and 71-72. G was administered for eight d following all doxorubicin cycles, and until neutrophil recovery following all Cyc and VP-16 cycles. Prophylactic antibiotics, anti-fungals, and septrin were administered for the duration of the study.

Results: 10 pts have been enrolled, 7 have completed therapy. There were no treatment-related deaths. One patient was removed on d 21 due to a transient decline in cardiac ejection fraction. Febrile neutropenia or infection complicated 11% of cycles (A-2/24; Cyc or VP-16 3/20). Platelet transfusions were required following 100% of Cyc cycles, but were not required after any A or VP-16 cycles. Grade III neuropathy occurred in 1 pt. Response has been evaluated in 7 pts, with 5 complete (CR) and 2 partial (PR) responses obtained. Five are currently progression free (29,20,13,9,1months(m) from enrolment). Two pts relapsed (12,2 m), 2 others are still on study.

Conclusions: This regimen is feasible. It is being expanded for a randomized trial.

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97-05 NHL STUDY

Phase I Trial of Escalating Dose DaunoXome(D) in combination with vincristine(O), cyclophosphamide(C) and prednisolone(P) as primary treatment for Elderly patients(pts) with non-Hodgkin’s Lymphoma(NHL): An Irish Clinical Oncology Research Group Study

D Fennelly, P Donnellan, R O'Donnell, M. O'Leary, KM Chan, J Ballot, D McCarthy B. Moulton, J Crown. Depts of Medical Oncology and Haematology, St. Vincent's Hospitals Group, and Beaumont Hospital, Dublin, Ireland. (Supported by Nextar Pharmaceuticals)

Aggressive NHL is a highly chemotherapy-sensitive neoplasm. The CHOP regimen which consists of doxorubicin (H), C, O and prednisolone(P) is widely used, but is too toxic for some elderly pts, or for those with poor performance status. H appears to be a major contributor to toxicity in these pts. D is a liposomally-encapsulated daunorubicin which may have a more favourable therapeutic index than H. Doses of 100-120mg/m2 were reported to be safe, and active in NHL. We performed a phase I trial to determine the dose-limiting toxicities and maximum-tolerated dose of D administered with C, O and P in pts with previously untreated NHL, as a D-containing CHOP variant.

Regimen: All pts received C 600mg/m2, V 2mg and P 60mg/day 8 days with a 6 day taper. Cohorts of pts received escalating doses of D, with no intra-patient escalation: Level I-80; Level II-100; Level III-120. Pts with Grade IV neutropenia received prophylactic ciprofloxacin.

Pts with stage I disease receive 4 cycles followed by RT, pts with higher stages receive 6 cycles.

Results: Total accrual was 12, median age 71 (58-78). There were no treatment-related deaths.

*Pt with progressive shrinkage of residual nodes 1 year post chemotherapy. Eval=Evaluable; FN= Febrile neutropenia; **complete or partial response or progression.

D infusion reactions were seen in 2 pts at Level III. D was safely re-instituted with antihistamines and longer infusion time.

Conclusions: (1) D can be safely combined with C, O and P in elderly pts. (2) No dose-limiting toxicities seen at D 120 mg/m2. (3) The regimen is active in NHL.