PACLITAXEL, CISPLATIN, ETOPOSIDE with concurrent XRT
PACLITAXEL 175 mg/m2 1-hour infusion DAY 1
CISPLATIN 50 mg/m2 IV over 2 hours DAY 1
ETOPOSIDE 100 mg/m2 IV over 30 minutes DAY 1
ETOPOSIDE 100 mg PO BID DAYS 2-5
TOTAL 5 CYCLES Q 3 WEEKS
TRT 42 Gy in 15 fractions concurrently with cycle 3
PCI administered to all who had CR at restaging 4 weeks after last cycle (total 30 Gy, 15 fractions).
Prophylaxis: Dexamethasone 20 mg po 12 hours & 30 minutes before paclitaxel administration, H2-blocker, H1-blocker
DAY 8 & 15 CBC check:
If WBC> 1.0 X 10e9/L, PMN> 0.5 X 10e9/L, PLT>75,000/uL then full dose
If WBC 0.5-1.0 X 10e9/L, PMN 0.3-0.5 X 10e9/L, PLT 50,000-75,000/uL then reduce paclitaxel & etoposide dose by 20%.
If WBC <0.5 X 10e9/L, PMN <0.3 X 10e9/L, PLT <50,000/uL then reduce paclitaxel & etoposide dose by 40%.
IF febrile leukopenia, then reduce paclitaxel & etoposide dose by 20%.
Ref: JCO 19:3533, 2001. N=39 Phase II; 74% had grade 3/4 leukopenia; 10% grade 3 thrombocytopenia. Grade 3 esophagitis 13%. ORR~92%; CR 81%; PR 11%. Median Survival 21 months.
Cisplatin 80 mg/m2 DAY 1
Etoposide 80 mg/m2 IV DAYS 1-3
REF- JCO 12: 2022,1994
Cytoxan 800-1000 mg/m2 IV Day 1
Doxorubicin 40-45 mg/m2 IV Day 1
Vincristine 1.4 mg/m2 IV Day 1
repeat Q21 days
J Nat Cancer Inst. 83: 855, 1991 (vs PE vs PE/CAV).
Cytoxan 1000 mg/m2 IV Day 1
Doxorubicin 45 mg/m2 IV Day 1
Etoposide 50 mq/m2 IV Days 1-5
Irinotecan 60 mg/m2 IV D1,8,15
Cisplatin 60 mg/m2 IV D1
REF: 346:85-91 January 10, 2002
N=154; Median survival 12.8 months (vs 9.4 in PE group P=0.002), At two years: 19.5% alive in Irinotecan+Cisplatin group (vs 5.2% in PE group).
Toxic effects were graded according to the JCOG Toxicity Criteria,7 in which a grade of 1 indicates a mild effect, grade 2 a moderate effect, grade 3 a severe effect, and grade 4 a life-threatening effect. Administration of irinotecan was skipped on day 8 or 15 if the leukocyte count was 2000 per cubic millimeter or less, if the platelet count was 50,000 per cubic millimeter or less, or if there was diarrhea. Administration of subsequent cycles of irinotecan was allowed when the leukocyte count reached at least 3500 per cubic millimeter, the platelet count reached at least 100,000 per cubic millimeter, and the diarrhea had subsided. The dose of irinotecan in subsequent cycles was reduced by 10 mg per square meter from the planned dose if there were grade 4 hematologic toxic effects or if grade 2 or 3 diarrhea developed. Treatment was discontinued in patients with grade 4 diarrhea.
Carboplatin AUC-6 DAY 1
Etoposide 80 mg/m2 DAYS 1-3
Paclitaxel 175 mg/m2 DAY 3
GCSF 5 ug/kg sq DAYS 4-1
REF: JCO 15: 3464, 1997
Etoposide 100 mq/m2 days 1-3
Carboplatin 450 mg/m2 IV day 1
REF-Acta Oncol. 33: 921, 1997
Etoposide 160 mg/m2/d PO days 1-5
repeat Q28 days
Etoposide 50 mg PO BID x 14 days
repeat Q21 days
REF: Seminars oncol 20:315, 1993
Taxol 250 mg/m2 over 24hrs day1
JCO 13:1430, 1995
Am J Clin Oncol. 22: 517, 1999
Topotecan 1.5-2.0 mg/m2/d. IV over 30 min days 1-5
repeat Q21 days
REF- JCO 17: 658, 1999
Phase III Study of Concurrent Versus Sequential Thoracic Radiotherapy in Combination With Cisplatin and Etoposide for Limited-Stage Small-Cell Lung Cancer: Results of the Japan Clinical Oncology Group Study 9104
To evaluate the optimal timing for thoracic radiotherapy (TRT) in limited-stage small-cell lung cancer (LS-SCLC), the Lung Cancer Study Group of the Japan Clinical Oncology Group conducted a phase III study in which patients were randomized to sequential TRT or concurrent TRT.
PATIENTS AND METHODS: We treated 231 patients with LS-SCLC. TRT consisted of 45 Gy over 3 weeks (1.5 Gy twice daily), and the patients were randomly assigned to receive either sequential or concurrent TRT. All patients received four cycles of cisplatin plus etoposide every 3 weeks (sequential arm) or 4 weeks (concurrent arm). TRT was begun on day 2 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm.
RESULTS: Concurrent radiotherapy yielded better survival than sequential radiotherapy (P = .097 by log-rank test). The median survival time was 19.7 months in the sequential arm versus 27.2 months in the concurrent arm. The 2-, 3-, and 5-year survival rates for patients who received sequential radiotherapy were 35.1%, 20.2%, and 18.3%, respectively, as opposed to 54.4%, 29.8% and 23.7%, respectively, for the patients who received concurrent radiotherapy. Hematologic toxicity was more severe in the concurrent arm. However, severe esophagitis was infrequent in both arms, occurring in 9% of the patients in the concurrent arm and 4% in the sequential arm.
CONCLUSION: This study strongly suggests that cisplatin plus etoposide and concurrent radiotherapy is more effective for the treatment of LS-SCLC than cisplatin plus etoposide and sequential radiotherapy.