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Preoperative chemotherapy for locally advanced non-small cell lung cancer
Abstracts/Lung
Cancer 11 (1994) 123-150
700 mg/mr over 14 days, all four patients experienced grade III or IV leukocytopenia, and two developed grade III stomatitis. No cumulative toxicity was observed. A steady concentration of etoposide was achieved 24 hours after the start of chemotherapy, and it was significantly correlated with surviving tractions of leukocytes (r = -64, P = .OOl) and platelets (r = -.68, P C .OOl). The leukocyte count at the termination of chemotherapy predicted the. nadii count (r = .93, P C .OOl). Conclusion: Stiy blood levelsof etoposide were maintained for prolongedperiods,during 14-daycontinuousinfusions.Leukocytopenia and stomatitis were dose&miting. Nadir counts and surviving fractions of leukocytes were predicted by the leokocyte count at the end of chemotherapy and the conceutmtion of etoposide, respectively. The recommendeddose for phase II trials is 600 mg/& over I4 days.
Combined treatment modalities Preoperative chemotherapy for locally advanced non-small cell lung cancer
Holmes EC, Ruckdeschel JC. Factor Building, UCLA School of Medicine, Los Angeles, CA 90024. Lung Cancer (Ireland) 1993;9 Suppl 2:S31-7. Recently, the field of preoperative chemotherapy for non-small cell lung cancer (NSCLC) has been the focus of Phase II trials. Extensive experience with preoperative therapy has been reported by such study groups as the Rush-Presbyterian group, Memorial Sloan-Kettering Cancer Center, the Dana Farber Institute, the University of Toronto, and the Lung Cancer Study Group. The studies by these and other investigative groups are reviewed here and, although all but one of the studies was flawed by the lack of a control arm, results are encouraging. Comparisonofdata fromthevarious studies isdifficult duetodiffemnces in preoperative staging, but it appears that 60- 75 % of patients may be expected to respond to one of a number of preoperative regimens, the majority of responders will be able to go on to surgical resection and about 10% of patients initially entered into a study are likely to attain histologic complete response, with correspondingly higher rates for those who undergo surgery. Toxicity rates are significant and survival data are not yet conclusive, however, and it is clear that a controlled trial is needed.
141
(n = 11) progressed. Squamous histologic type was predictive of resectability, 18 of 20 patients having resectable squamous cell tumors (p c 0.05). Actuarial survivals at 1 and 2 years were 74% and 52%. respectively. ~npatientswithresectabletumorssurvivalsat 1 and 2year~ were 85 % and 67 % , respectively. For those with unresectable lesions, survivals were 43 96 and 14 % . Relapse- free survivals at 1 and 2 years for patients with resectable lesions were 70% and 42%, respectively. Relapses were local in 25 % (n = 4), at a distant site only in 50% (n = 8). combined local and distant in 25 % (n = 4). Distant relapse Occurred in the central nervous system only in 7 of 8 patients (88 %). Complete resectability was highly predictive of improved survival @ < 0.0002). Weight loss did not affect resectability but was associated with decreased survival (p < 0.003). Neoadjuvant chemotherapy appears to improve resectability and to pathologically downstage N2 non-small-ceil lung cancer from stage IIIA. Multiinstitutional randomized trials are needed to further demonstrate the efficacy of this approach.
Adjuvant chemotherapy for completely resected stage111nonsmall-cell lung cancer: Results of a randomized prospective study Ohta M, Tsuchiya R, Shimoyama M, Sawamura K, Mori T, Miyamwa N et al. National Kyushu Cancer Center, 3-l-l. Notame, Uinami-ku, Fukuoko 815, J Thorac Cardiovasc Surg 1993;106:703-8. Two hundred nine patients with completely resected stage III nonsmall- cell lung cancer were random&d to receive postoperative cisplatin and vindesine chemotherapy or no further treatment. Before randomization, patients were stratified by the histologic characteristics of their tumors (squamous versus nonsquamous cell carcinoma). Prognostic variables such as histology, performance status, extent of operation, and tumor and nodal status of the eligible patients in chemotherapy (n = 90) and control groups (n = 91) were equally distributed. There was no statistically significant difference in diseasefree and overall survival between the two groups. The 3-year diswaefree survivals of the chemotherapy and control groups were 37 46 and 42 96, respectively. The median survival times (S-year smvival) were 31 months (35 W) in the chemotherapy group and 37 months (41 W) in the control group. These was no different pattern in the first site of recurrence (local versus systemic) between the two groups. This study failed to demonstrate the therapeutic benefits of postoperative cisplatin and vindesine chemotherapy.
Multimodality therapy of patients with stage WA, NZ nonsmall-cell lung cancer: Impact of preoperative chemotherapy on reaectahility and downstaging
Carboplatin, etoposide, and radiotherapy, followed by surgery, for the treatment of marginally resectable non-small cell lung cancer
Kim DH, Lynch TJ, Mentxer SJ, Lee TH, Strauss GM, Elias AD et al. Division of lhoracic Surgery, Brigham and Women’s Hospital, 75 Fran&d., Boston, MAO2115. JThoracCardiovascSurg 1993;106:6%702. To assess the effect of neoadjuvant platinum-based chemotherapy on resectability, stageofdiseaseatresection, andpattemsofrecurrenceand survival in patients with IIIA, N2 non-small-cell lung cancer, we examined the first 60 patients treated with neoadjuvant chemotherapy followed by attempted resection in our institution. Of 67 patients identified, 7 patients were ineligible because of comorbidities, 3 patientsreliisedchemotherapy, and 1 consented butdiedbeforetreatment. Fifty-six received neoadjuvant chemotherapy. Complications of chemotherapy were minor, with no deaths. Fifty-four patients had thoracotomy; 75 % (n = 42) had complete resection and 25 % (n = 14) had unresectable lesions. One postoperative death occurred (2%). Pathologic review of specimens and nodal groups revealed that 41% (n = 23) were downstaged, 39 96 (n = 22) remained stage IIIA, and 19 %
Deutsch MA, Leopoldt KA, Crawford J, Wolfe W, Foster W, Blackwell S et al. Department of Medicine, Duke University Medical Center, Durham. NC 27710. Gxncer Treat Rev 1993;19 Suppl C:53-62. The present study was undertaken in order to determine the feasibility and efficacy of induction chemotherapy with carboplatin and etoposide, followed by weekly carboplatin and full-course radiotherapy as pre-operative therapy for marginally resectable non-smell cell lung cancer (NSCLC). Twenty-eight patients with good Eastern Cooperative Oncology Group (ECGG) performance status ratings and stage IIIA NSCLC received induction chemotherapy with carboplatin (dose computed with the Egorin formula, days 1 and 29) and etoposide (100 mg/mr/day, days I through 3 and 29 through 31). This was followed by 100 mglmr weekly carboplatin given over 6 weeks, concurrently with 60 Gy radiotherapy. Patients with either responsive or stable disease underwent thoracotomy 4 weeks at?er the completion of combinedmodality therapy. All 29 patients received the first chemotherapy cycle (average carboplatin dose, 407 mg/m$ range, 195 to 586 mglmr).
Cancer 11 (1994) 123-150
700 mg/mr over 14 days, all four patients experienced grade III or IV leukocytopenia, and two developed grade III stomatitis. No cumulative toxicity was observed. A steady concentration of etoposide was achieved 24 hours after the start of chemotherapy, and it was significantly correlated with surviving tractions of leukocytes (r = -64, P = .OOl) and platelets (r = -.68, P C .OOl). The leukocyte count at the termination of chemotherapy predicted the. nadii count (r = .93, P C .OOl). Conclusion: Stiy blood levelsof etoposide were maintained for prolongedperiods,during 14-daycontinuousinfusions.Leukocytopenia and stomatitis were dose&miting. Nadir counts and surviving fractions of leukocytes were predicted by the leokocyte count at the end of chemotherapy and the conceutmtion of etoposide, respectively. The recommendeddose for phase II trials is 600 mg/& over I4 days.
Combined treatment modalities Preoperative chemotherapy for locally advanced non-small cell lung cancer
Holmes EC, Ruckdeschel JC. Factor Building, UCLA School of Medicine, Los Angeles, CA 90024. Lung Cancer (Ireland) 1993;9 Suppl 2:S31-7. Recently, the field of preoperative chemotherapy for non-small cell lung cancer (NSCLC) has been the focus of Phase II trials. Extensive experience with preoperative therapy has been reported by such study groups as the Rush-Presbyterian group, Memorial Sloan-Kettering Cancer Center, the Dana Farber Institute, the University of Toronto, and the Lung Cancer Study Group. The studies by these and other investigative groups are reviewed here and, although all but one of the studies was flawed by the lack of a control arm, results are encouraging. Comparisonofdata fromthevarious studies isdifficult duetodiffemnces in preoperative staging, but it appears that 60- 75 % of patients may be expected to respond to one of a number of preoperative regimens, the majority of responders will be able to go on to surgical resection and about 10% of patients initially entered into a study are likely to attain histologic complete response, with correspondingly higher rates for those who undergo surgery. Toxicity rates are significant and survival data are not yet conclusive, however, and it is clear that a controlled trial is needed.
141
(n = 11) progressed. Squamous histologic type was predictive of resectability, 18 of 20 patients having resectable squamous cell tumors (p c 0.05). Actuarial survivals at 1 and 2 years were 74% and 52%. respectively. ~npatientswithresectabletumorssurvivalsat 1 and 2year~ were 85 % and 67 % , respectively. For those with unresectable lesions, survivals were 43 96 and 14 % . Relapse- free survivals at 1 and 2 years for patients with resectable lesions were 70% and 42%, respectively. Relapses were local in 25 % (n = 4), at a distant site only in 50% (n = 8). combined local and distant in 25 % (n = 4). Distant relapse Occurred in the central nervous system only in 7 of 8 patients (88 %). Complete resectability was highly predictive of improved survival @ < 0.0002). Weight loss did not affect resectability but was associated with decreased survival (p < 0.003). Neoadjuvant chemotherapy appears to improve resectability and to pathologically downstage N2 non-small-ceil lung cancer from stage IIIA. Multiinstitutional randomized trials are needed to further demonstrate the efficacy of this approach.
Adjuvant chemotherapy for completely resected stage111nonsmall-cell lung cancer: Results of a randomized prospective study Ohta M, Tsuchiya R, Shimoyama M, Sawamura K, Mori T, Miyamwa N et al. National Kyushu Cancer Center, 3-l-l. Notame, Uinami-ku, Fukuoko 815, J Thorac Cardiovasc Surg 1993;106:703-8. Two hundred nine patients with completely resected stage III nonsmall- cell lung cancer were random&d to receive postoperative cisplatin and vindesine chemotherapy or no further treatment. Before randomization, patients were stratified by the histologic characteristics of their tumors (squamous versus nonsquamous cell carcinoma). Prognostic variables such as histology, performance status, extent of operation, and tumor and nodal status of the eligible patients in chemotherapy (n = 90) and control groups (n = 91) were equally distributed. There was no statistically significant difference in diseasefree and overall survival between the two groups. The 3-year diswaefree survivals of the chemotherapy and control groups were 37 46 and 42 96, respectively. The median survival times (S-year smvival) were 31 months (35 W) in the chemotherapy group and 37 months (41 W) in the control group. These was no different pattern in the first site of recurrence (local versus systemic) between the two groups. This study failed to demonstrate the therapeutic benefits of postoperative cisplatin and vindesine chemotherapy.
Multimodality therapy of patients with stage WA, NZ nonsmall-cell lung cancer: Impact of preoperative chemotherapy on reaectahility and downstaging
Carboplatin, etoposide, and radiotherapy, followed by surgery, for the treatment of marginally resectable non-small cell lung cancer
Kim DH, Lynch TJ, Mentxer SJ, Lee TH, Strauss GM, Elias AD et al. Division of lhoracic Surgery, Brigham and Women’s Hospital, 75 Fran&d., Boston, MAO2115. JThoracCardiovascSurg 1993;106:6%702. To assess the effect of neoadjuvant platinum-based chemotherapy on resectability, stageofdiseaseatresection, andpattemsofrecurrenceand survival in patients with IIIA, N2 non-small-cell lung cancer, we examined the first 60 patients treated with neoadjuvant chemotherapy followed by attempted resection in our institution. Of 67 patients identified, 7 patients were ineligible because of comorbidities, 3 patientsreliisedchemotherapy, and 1 consented butdiedbeforetreatment. Fifty-six received neoadjuvant chemotherapy. Complications of chemotherapy were minor, with no deaths. Fifty-four patients had thoracotomy; 75 % (n = 42) had complete resection and 25 % (n = 14) had unresectable lesions. One postoperative death occurred (2%). Pathologic review of specimens and nodal groups revealed that 41% (n = 23) were downstaged, 39 96 (n = 22) remained stage IIIA, and 19 %
Deutsch MA, Leopoldt KA, Crawford J, Wolfe W, Foster W, Blackwell S et al. Department of Medicine, Duke University Medical Center, Durham. NC 27710. Gxncer Treat Rev 1993;19 Suppl C:53-62. The present study was undertaken in order to determine the feasibility and efficacy of induction chemotherapy with carboplatin and etoposide, followed by weekly carboplatin and full-course radiotherapy as pre-operative therapy for marginally resectable non-smell cell lung cancer (NSCLC). Twenty-eight patients with good Eastern Cooperative Oncology Group (ECGG) performance status ratings and stage IIIA NSCLC received induction chemotherapy with carboplatin (dose computed with the Egorin formula, days 1 and 29) and etoposide (100 mg/mr/day, days I through 3 and 29 through 31). This was followed by 100 mglmr weekly carboplatin given over 6 weeks, concurrently with 60 Gy radiotherapy. Patients with either responsive or stable disease underwent thoracotomy 4 weeks at?er the completion of combinedmodality therapy. All 29 patients received the first chemotherapy cycle (average carboplatin dose, 407 mg/m$ range, 195 to 586 mglmr).