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Biomedical subjects

C J Langer

Publications and source records attributed to C J Langer.

At least 19 recordsLinked to original sources
PubMed2001

Phase II radiation therapy oncology group trial of weekly paclitaxel and conventional external beam radiation therapy for supratentorial glioblastoma multiforme.

PURPOSE: Fractionated external beam radiotherapy (EBRT) +/- carmustine (BCNU) is the standard of care for patients with glioblastoma multiforme (GBM), but survival results remain poor. Preclinical studies indicate synergy between RT and paclitaxel (TAX) in astrocytoma cell lines. Phase I studies in GBM have demonstrated a maximum tolerated dose for TAX of 225 mg/m(2)/3 h/week x 6, during EBRT, with no exacerbation of typical RT-induced toxicities. The Radiation Therapy Oncology Group (RTOG) therefore mounted a Phase II study to determine the feasibility and efficacy of conventional EBRT and concurrent weekly TAX at its MTD. PATIENTS AND METHODS: Sixty-two patients with histologic diagnosis of GBM were enrolled from 8/16/96 through 3/21/97 in a multi-institutional Phase II trial of EBRT and TAX 225 mg/m(2)/3 h (1-3 h before EBRT), administered the first treatment day of each RT week. Total EBRT dose was 60 Gy (200 cGy/fraction), 5 days per week. A smaller treatment field, to include gross disease plus a margin only, was used after 46 Gy. RESULTS: Sixty-one patients (98%) were evaluable. Median age was 55 years (range, 28-78). Seventy-four percent were > or = 50 years. Recursive partitioning analysis (RPA) Classes III, IV, V, VI included 10 (17%), 21 (34%), 25 (41%), and 5 (8%) patients, respectively. Gross total resection was performed in only 16%. There was no Grade 3 or 4 neutropenia or thrombocytopenia. Hypersensitivity reactions precluding further use of TAX occurred in 4 patients. There were 2 instances of late neurotoxicity (4% Grade 3 or 4). Ninety-one percent of patients received treatment per protocol. Seventy-seven percent completed prescribed treatment (6 weeks). Of 35 patients with measurable disease, CR/PR was observed in 23%, MR in 17%, and SD in 43%. Seventeen percent demonstrated progression at first follow-up. Median potential follow-up time is 20 months. Median survival is 9.7 months, with median survivals for RPA classes III, IV, V, and VI of 16.3, 10.2, 9.5, 2.5 months, respectively. Ten patients remain alive. CONCLUSION: Concurrent full-dose EBRT and weekly high-dose TAX is feasible in the majority of GBM patients. Acute toxicity is acceptable; myelosuppression and peripheral sensory neuropathy are surprisingly modest, despite considerably higher overall dose intensity, compared to that achievable in other disease sites. Median survival by RPA class without prolonged adjuvant therapy is comparable to RTOG controls treated with standard EBRT and BCNU (1 year of BCNU).

Adult↗
PubMed2001

The role of UFT and the combination of UFT/leucovorin in non-small cell lung cancer.

Although 5-FU administered as a single agent in different intravenous bolus schedules has been shown to have minimal activity in non-small cell lung cancer (NSCLC), several lines of experimental evidence suggest that 5-FU in combination regimens may be synergistic with the 'anchor' drug of the combination. Moreover, the recent availability of oral formulations of 5-FU together with the ability to modulate the anabolic and catabolic metabolism of 5-FU with leucovorin and dihydropyrimidine dehydrogenase (DPD) inhibitors, respectively, may provide a substantial improvement in the ease of administration and the efficacy of fluoropyrimidine therapy. Several oral fluoropyrimidines are under investigation. Orzel [UFT (uracil:tegafur) plus oral leucovorin] is the first oral DPD-inhibitory fluoropyrimidine. Orzel administered daily achieves similar concentrations of 5-FU obtained with continuous-infusion 5-FU. This paper reviews the clinical experience with UFT and Orzel in the treatment of NSCLC.

Administration, Oral↗
PubMed2001

Induction and concurrent paclitaxel/carboplatin every 3 weeks with thoracic radiotherapy in locally advanced non-small-cell lung cancer: an interim report.

The paclitaxel/carboplatin combination has demonstrated promising activity in metastatic non-small-cell lung cancer (NSCLC); therefore, we mounted an exploratory study of these agents with thoracic radiation (TRT) in locally advanced NSCLC. Eligibility stipulated a Karnofsky performance status >or= 70%, weight loss or= 2 esophagitis has corresponded to length (> 16 cm) of esophagus in the radiation treatment field (Fisher's exact test, P = 0.006). The partial response rate to induction therapy was 40% and to the combined modality therapy was 60%. The median survival for all 49 patients is 15.3 months, with a median disease-free survival (DFS) of 7.8 months. In the subset of 22 patients treated on the phase I portion of the study, the median survival and DFS were 18.5 months and 13.5 months, respectively. Induction therapy with paclitaxel and carboplatin followed by concurrent chemoradiotherapy with the same agents is an active and well-tolerated treatment approach in locally advanced NSCLC. To date, paclitaxel 175 mg/m2 plus carboplatin AUC 5 administered at 3-week intervals for 2 cycles is safe in combination with TRT.

Journal Article↗
PubMed2001

Weekly irinotecan and cisplatin in advanced non-small cell lung cancer: a multicenter phase II study.

The combination of weekly irinotecan (CPT-11) and monthly cisplatin has shown promising activity in advanced non-small cell lung cancer (NSCLC) in previous Phase I and II studies. However, same-day administration of these agents may better exploit their therapeutic synergy and minimize toxicities. This multicenter Phase II study was undertaken to evaluate the efficacy and safety of a combination of weekly CPT-11 and weekly cisplatin in patients with advanced NSCLC. Patients with chemotherapy-naive stage IIIB or IV NSCLC were treated with repeated cycles of therapy comprising weekly treatment with both cisplatin and CPT-11 for 4 weeks, followed by a 2-week rest. The starting doses of CPT-11 and cisplatin were 65 and 30 mg/m2, respectively. Treatment was continued until the occurrence of disease progression, unacceptable toxicity, or a maximum of six cycles. Fifty patients were enrolled. The median age was 59 years (range, 44-79 years). Eastern Cooperative Oncology Group performance status was 0 in 22 patients, 1 in 19 patients, and 2 in 9 patients. Seven and 43 patients had stages IIIB and IV disease, respectively. Five patients had brain metastasis. Patients received a median of three 6-week cycles (range, 1-6). The objective response rate was 36% (18 of 50; 95% confidence interval, 24-54%) and included 18 partial responses. Median time to tumor progression was 6.9 months (range, 0.6-15.2). The median survival was 11.6 months (range, 0.16-21.9 months), and the 1-year survival rate was 46%. Grade 3/4 nonhematological toxicities included vomiting (12%) and diarrhea (26%). Grade 3/4 hematological toxicities included anemia (14%), neutropenia (26%), and thrombocytopenia (14%). Relative dose intensities for CPT-11 and cisplatin were 89 and 62%, respectively. Weekly combined administration of CPT-11 and cisplatin achieved a promising overall response rate, median time to tumor progression, and median survival in patients with stage IIIB/IV NSCLC. The regimen was well tolerated, and the planned dose intensity was well maintained. Further evaluation of this combination in NSCLC is warranted.

Adult↗
PubMed2001

Treatment of non-small-cell lung cancer in North America: the emerging role of irinotecan.

Topoisomerase I inhibitors have demonstrated significant activity in non-small-cell lung cancer. In phase II studies, particularly in Japan, single-agent irinotecan (Camptosar, CPT-11) has produced response rates as high as 35%. In combinations with cisplatin (Platinol), it has also resulted in overall response rates of 41% to 52%, with median survival of 10.2 to 13 months, and 1-year survival rates of 33% and 58%. A Japanese phase III randomized trial of irinotecan, either alone or in combination with cisplatin vs vindesine/cisplatin in previously untreated stage IIIB/IV non-small-cell lung cancer, demonstrated that survival among stage IV patients was significantly better in the irinotecan arms compared to the vindesine/cisplatin group. However, another Japanese phase III study comparing irinotecan/cisplatin to vindesine/cisplatin failed to show a survival difference. Initial North American efforts recapitulated this work, while a follow-up study incorporated weekly irinotecan with weekly cisplatin, yielding a response rate of 36%, median survival of 11.6 months, and a 1-year survival rate of 46%. Irinotecan/taxane combinations have also shown promise. Phase I/II studies in advanced non-small-cell lung cancer with paclitaxel (Taxol), irinotecan, and carboplatin (Paraplatin) produced a response rate of 38%, median survival of 11 months, and a 1-year survival rate of 47%; other trials with irinotecan and paclitaxel are ongoing. Phase I data for irinotecan/docetaxel (Taxotere) have indicated an overall response rate of 32%, median survival of 39 weeks, and a 1-year survival rate of 38%; subsequent phase II trials used either cisplatin or irinotecan in combination with docetaxel and yielded a promising median survival of 45.6 weeks, comparable to the standard cisplatin/docetaxel combination. Phase I trials with irinotecan and gemcitabine (Gemzar) have also yielded promising results. Follow-up efforts include phase II studies in both chemonaive advanced non-small-cell lung cancer and progressive small-cell lung cancer (salvage therapy). Clearly, clinical trial data have demonstrated the utility of irinotecan in the treatment of advanced non-small-cell lung cancer. Planned combinations with new chemotherapeutic agents and biological response modifiers may provide additional treatment options.

Antineoplastic Agents↗
PubMed2001

The emerging world role of irinotecan in lung cancer.

Irinotecan (CPT-11, Camptosar), either alone or in combination with cisplatin (Platinol), has demonstrated activity in advanced non-small-cell lung cancer (NSCLC). In single-agent studies, response rates as high as 35% have been observed; in combination with cisplatin, response rates have ranged as high as 50%, with 1-year survival rates of 33% to 58%. A critical phase III randomized trial comparing irinotecan, either alone or in combination with cisplatin, to vindesine/cisplatin, demonstrated superior survival for stage IV patients receiving irinotecan. The first North American effort to replicate the schedule used in the phase III trial (cisplatin 80 mg/m2 and irinotecan 60 mg/m2 on days 1, 8, and 15 every month) yielded a response rate of 29%, median survival time of nearly 10 months, and 1-year survival rate of 37%. A subsequent multi-institutional trial conducted through Vanderbilt Cancer Center Affiliate Network and Fox Chase Cancer Center combined both agents on a weekly schedule in an attempt to exploit their putative synergy and to potentially decrease toxicity. This schedule, which employed irinotecan 65 mg/m2 and cisplatin 30 mg/m2 both weekly x 4, was better tolerated than the monthly cisplatin combination with a higher response rate (36%), median survival (11.6 months), and 1-year survival rate (46%). Multiple phase I and phase II studies have combined irinotecan with taxanes, either alone or in concert with carboplatin (Paraplatin), yielding similar response and survival rates. Finally, a critical phase III trial from Japan has demonstrated superior outcome for irinotecan and cisplatin vs standard etoposide/cisplatin in the treatment of extensive small-cell carcinoma of the lung. At least one North American trial will determine if these results are reproducible.

Antineoplastic Agents↗
PubMed2000

The role of new agents in advanced non-small-cell lung carcinoma.

Over the past 5 to 7 years, new and promising systemic agents have entered the therapeutic armamentarium in the treatment of advanced non-small-cell lung cancer. In particular, the taxanes, irinotecan, vinorelbine, and gemcitabine, have each been shown to perturb the natural history of this disease. In combination with cisplatin, these agents have yielded improvements in response rates and in survival, compared with either cisplatin alone or with older platinum combinations, with consistent 1-year survival rates of 30% to 40% or more and response rates exceeding 25%. Other factors may also be responsible for improved survival rates, including patient selection, improved supportive care, and more extensive screening procedures, such as CT and positron emission tomography, which have resulted in stage migration. Future directions will focus on the role of nonplatinum combinations, particularly in the elderly and in patients with compromised performance status; salvage therapy in patients with intact performance status; quality of life and quality adjusted survival; and the role of new biologic agents, which alter the tumor milieu and may be readily integrated into standard cytotoxic regimens. Except for unfit or unwilling patients, there is no room for therapeutic nihilism.

Adult↗
PubMed2000

Phase II trial of induction high-dose chemotherapy followed by surgical resection and radiation therapy for patients with marginally resectable non-small cell carcinoma of the lung.

The combination of carboplatin and paclitaxel is an active regimen in non-small cell lung cancer (NSCLC). Historically, patients with stage III disease have manifested higher response rates than patients with metastatic disease, and patients achieving a pathologic complete response to induction chemoradiation therapy prior to surgery have shown better long-term outcome. Based upon our pilot data using high-dose carboplatin and paclitaxel, we designed a phase II trial in patients with marginally resectable stage IIIA NSCLC. Ten patients, with bulky nodal stage IIIA disease, initially received etoposide (2 g/m2) and granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSC). Two cycles, 28 days apart, of carboplatin (AUC 12 in seven patients; AUC 16 in three patients) and paclitaxel (250 mg/m2) were administered with filgrastim (5 microg/kg) and PBSC support. After re-evaluation, patients underwent a thoracotomy followed by radiotherapy (44-60 Gy) if deemed resectable, or radiotherapy alone (60 Gy) if not resectable. The median age was 58.5 years (48-66) with a median ECOG performance status of 0 (0-1). Histology was adenocarcinoma in seven patients; the remainder had either squamous cell, large cell or bronchoalveolar carcinoma. Based on CT radiography, the overall response rate was 40%. Eight of ten patients underwent resection with four right pneumonectomies, three right upper lobectomies and one wedge resection of the right upper lobe. Six patients had a complete resection. Of eight patients resected, four were downstaged by induction therapy, three remained unchanged and one was found to have more extensive disease. The remaining two patients developed metastatic disease while receiving chemotherapy. The median dose of postoperative radiotherapy was 54 Gy (35-66 Gy). Actual median follow-up for all patients was 89 weeks (25 to 136+). The actuarial median overall survival was 124 weeks (25 to 136+) and time to progression was 57 weeks (17 to 136+). The median dose of carboplatin delivered expressed as mg/m2 was 779 (615-1540). Neutropenic fever occurred in two patients during the initial mobilization cycle only. The median number of units of RBC and/or platelets transfused was 0 (0-2 and 0-6, respectively). There were no significant non-hematologic toxicities. High-dose induction chemotherapy with stem cell rescue is feasible and safe with an acceptable response rate. Thoracotomy, including pneumonectomy and postoperative radiotherapy, were well tolerated by patients after undergoing high-dose induction chemotherapy with no apparent increase in peri-operative morbidity. The pathologic complete response rate was low--one out of ten patients. These results indicate that dose escalation of induction chemotherapy does not improve response rates even in this highly selected patient population. Accordingly, the complexity and potential toxicity of high-dose chemotherapy, as delivered in this trial as neoadjuvant treatment of non-small cell lung cancer, is not warranted.

Adenocarcinoma↗
PubMed2000

Paclitaxel by 1-h infusion in combination with carboplatin in advanced non-small cell lung carcinoma (NSCLC).

In our previous study, FCCC 93-024, paclitaxel by 24-h infusion combined with carboplatin yielded a response rate of 62% and median survival of 54 weeks in advanced non-small cell lung cancer (NSCLC). Myelosuppression proved dose-limiting, requiring the routine use of granulocyte-colony stimulating factor (G-CSF). Based on the reported activity of 1-h paclitaxel infusion in NSCLC and minimal myelosuppression at doses of 135 and 200 mg/m2 every 3 weeks and the suggestion of a dose-response relationship, we launched an intrapatient dose escalation trial of combination carboplatin and 1-h paclitaxel. Chemotherapy-naïve patients with advanced NSCLC received paclitaxel 175 mg/m2 1-h and carboplatin dosed to a fixed targeted area under the concentration-time curve (AUC) of 7.5 at three weekly intervals for six cycles. In the absence of grade 4 myelosuppression, paclitaxel was escalated by 35 mg/m2/cycle on an intrapatient basis to a maximum dose of 280 mg/m2 by cycle 4. G-CSF was not routinely used. 57 patients (pts) were accrued from November 1994 through to April 1996. 44 pts (77%) had Eastern Cooperative Oncology Group (ECOG) performance status 1. Median age was 64 (range: 34-80) years. Cumulative peripheral sensory neuropathy proved dose-limiting and prohibitive in the first 20 evaluable patients (cohort A): grade > or = 1 in 15 patients (75%), grade 3 in 6 (30%), generally occurring at paclitaxel doses > or = 215 mg/m2 and obligating 3 patients to have treatment halted in the absence of disease progression. The protocol, therefore, was revised and the initial paclitaxel dose reduced to 135 mg/m2 with intrapatient dose escalation of 40 mg/m2/cycle to a maximum dose of 215 mg/m2, recapitulating the original dosing schema used in FCCC 93-024. 35 patients were enrolled in this second cohort (B); 33 proved evaluable. Whilst 17 (52%) experienced peripheral sensory neuropathy, grade 3 neurotoxicity developed in only 3 (9%). Myelosuppression also was less pronounced, with 42% exhibiting grade 4 granulocytopenia and 30% grade > or = 3 thrombocytopenia in cohort B compared with 70% and 50%, respectively in cohort A. Of the first 22 patients accrued to cohort A, 12 (55%) had major objective responses. Median survival was 48.5 weeks, 1-year survival rate 45% and 2-year survival rate 18%. Of 33 evaluable patients in cohort B, 9 (27%) had major objective responses. Median survival was 46 weeks, 1-year survival rate 47% and 2-year survival rate 12%. Combination paclitaxel by 1-h infusion and carboplatin at a fixed targeted AUC of 7.5 is active in advanced NSCLC. Neurotoxicity, not myelosuppression, proved dose-limiting at paclitaxel doses exceeding 215 mg/m2. Lower doses may be associated with lower response rates, but do not appear to compromise survival.

Adult↗
PubMed2000

Advanced non-small cell lung carcinoma: the emerging role of docetaxel.

The treatment of advanced non-small cell lung carcinoma (NSCLC) has improved greatly over the past decade. With the advent of new agents, in particular taxanes, gemcitabine, vinorelbine, and topoisomerase I inhibitors, response rates have improved from 15-20% to 25-35%, with commensurate improvement in median and one year survival rates to 8-10 months and 35-45%, respectively. These improvements have proven statistically significant in multiple studies [1-4]. Docetaxel, either alone or in combination with platinols, has shown particular promise; and, in some arenas, it has become a standard component of our therapeutic armamentarium. We will review the preclinical data and single agent activity of docetaxel in treatment-naive and previously treated NSCLC patients, its activity in combination with cisplatin and carboplatin, as well as other new agents, and finally focus on ongoing studies evaluating its role in locally advanced disease.

Animals↗
PubMed2000

Phase I pharmacokinetic trial of perillyl alcohol (NSC 641066) in patients with refractory solid malignancies.

Perillyl alcohol (POH) is a monoterpene with anticarcinogenic and antitumor activity in murine tumor models. Putative mechanisms of action include activation of the transforming growth factor beta pathway and/or inhibition of p21ras signaling, leading to differentiation or apoptosis. In this Phase I trial, 17 patients took POH p.o. three times daily for 14 days of each 28-day cycle. The starting dose of POH was 1600 mg/m2/dose, with escalations to 2100 and 2800 mg/m2/dose in subsequent cohorts. Chronic nausea and fatigue were dose-limiting toxic effects at 2800 mg/m2. Grade 1-2 hypokalemia was common at 2100 and 2800 mg/m2. Although POH could not be detected in plasma, two of its metabolites, dihydroperillic acid (DHPA) and perillic acid (PA), were measured in plasma and urine on days 1 and 15 after the first and last doses of POH, respectively. Both area under the concentration versus time curve and peak plasma concentration (Cmax) values increased with dose and exhibited high intersubject variability. Day 15 DHPA Cmax values ranged from a mean +/- SD of 22.6+/-12 microM at 1600 mg/m2/dose to 42.4+/-15.24 microM at 2800 mg/m2/dose. Corresponding mean +/- SD Cmax values for PA were 433.2+/-245.8 and 774.1+/-439.6 microM. One patient treated at the 2800 mg/m2/dose had markedly prolonged plasma levels of both PA and DHPA and developed grade 3 mucositis. POH treatment did not consistently alter the expression of p21ras, rap1, or rhoA in peripheral blood mononuclear cells obtained from patients treated at the highest dose level. The metabolites PA and DHPA did not change expression or isoprenylation of p21ras in MCF-7 breast or DU145 prostate carcinoma cells at concentrations that exceeded those achieved in patient plasma after POH treatment. We conclude that POH at 1600-2100 mg/m2 p.o. three times daily is well tolerated on a 14-day on/14-day off dosing schedule. Inhibition of p21ras function in humans is not likely to occur after POH administration at safe doses of the present oral formulation.

Administration, Oral↗
PubMed1999

The role of tegafur/uracil in pulmonary malignancy.

Tegafur/uracil (UFT) is an oral fluorinated pyrimidine composed of a combination of uracil and tegafur in a 4:1 molar ratio. When given on a continuous basis, it yields a fluorouracil area under the concentration-time curve identical to that achieved with isomolar concentrations of fluorouracil administered by continuous infusion. Its 8.7% response rate in advanced non-small cell lung cancer (NSCLC) is modest, but it has demonstrated synergy with cisplatin in human solid tumour xenografts. In combination with cisplatin in patients with advanced NSCLC, response rates of 29 to 43% were observed with acceptable toxicity. Researchers in Japan have demonstrated the utility of this agent as adjuvant therapy after surgical resection, either alone or in combination with cisplatin and vindesine versus observation; long term survival rates exceed 60%, compared with 49% for the control group. Efforts in the US will assess the role of this agent as non-cross-resistant consolidation therapy after a plateau in response has been obtained with platinum-based therapy in advanced disease. They will also recapitulate the Japanese studies, assessing their utility as adjuvant therapy in NSCLC patients who have undergone resection. Finally, ongoing phase I studies are combining this agent with paclitaxel and other systemic agents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Gemcitabine and carboplatin in combination: an update of phase I and phase II studies in non-small cell lung cancer.

Gemcitabine has demonstrated single-agent activity in advanced, incurable non-small cell lung cancer, yielding response rates of > or =20%. In combination with cisplatin, response rates of 30% to 60% and encouraging survival have been observed. Carboplatin causes much less nonhematologic toxicity than cisplatin. In a phase III Eastern Cooperative Oncology Group trial, initial therapy with carboplatin yielded superior survival in advanced non-small cell lung cancer compared with cisplatin combinations and other cisplatin analogs, despite a lower response rate. Thus, studies designed to identify optimal dose schedules for a combination of gemcitabine plus carboplatin are clearly warranted. Carmichael et al from the United Kingdom have identified a maximum tolerated dose of carboplatin of area under the curve of 5.2 mg/mL/min administered on day I followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle. This combination produced a response rate of 31% and a median survival of 10.5 months in 13 evaluable patients. A subsequent phase I evaluation reversing the carboplatin and gemcitabine sequence (gemcitabine preceding carboplatin on day 1) demonstrated no difference in toxicities, pharmacodynamics, or maximum tolerated dose. Other investigators have identified similar promising results with this regimen, although one North American investigator has observed untoward toxicity in a small number of patients using a standard 28-day dose schedule with gemcitabine administered on days, 1, 8, and 15. Day-15 gemcitabine dosing is problematic and may contribute to excessive thrombocytopenia when gemcitabine is combined with carboplatin. The ongoing phase I/II trials reviewed here have focused on a compressed 21-day schedule, with carboplatin administered every 3 weeks and gemcitabine given on days 1 and 8 only.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Concurrent chemoradiation using paclitaxel and carboplatin in locally advanced non-small cell lung cancer.

Evidence suggests that locally advanced non-small cell lung cancer may be more effectively treated with induction chemotherapy followed by radiation or concurrent chemoradiation compared with radiation alone. The majority of combined modality regimens evaluated in mature clinical trials incorporated cisplatin-based combinations, but none has incorporated newer active systemic agents or fully examined the potential role of induction chemotherapy followed by concurrent chemoradiation. The Fox Chase Cancer Center and its affiliate network have evaluated induction chemotherapy with paclitaxel plus carboplatin with or without granulocyte colony-stimulating factor priming followed by concurrent systemic chemotherapy and radiation therapy in patients with locally advanced non-small cell lung cancer. The regimen has been well-tolerated and paclitaxel dose escalation continues. The major response to combined therapy was 55% in the first 38 evaluable patients, and the 1-year survival rate is 72%. Median survival is 15 months. The primary toxicity following induction therapy has been myelotoxicity, which has been mild in severity. During concurrent therapy, the major toxicity has been esophagitis; only limited nonhematologic toxicity has been observed. Other studies evaluating different chemoradiation regimens have reported varying results. Paclitaxel/carboplatin-based combinations, administered cyclically at or near full systemic dose in combination with radiation, are feasible. Randomized studies are needed to determine the proper sequencing, potential survival benefits, and relative safety profiles of these combined modality regimens.

Adult↗
PubMed1999

Induction or neoadjuvant therapy in resectable non-small cell lung cancer.

Many patients with stage I-IIIA non-small cell lung cancer (NSCLC) resected for cure will experience distant relapse. Results of adjuvant chemotherapy trials after surgery have generally been negative. Neoadjuvant or induction chemotherapy before surgery offers several theoretical advantages; the results of neoadjuvant chemotherapy or combined chemoradiation therapy followed by surgery in resectable and potentially resectable NSCLC are reviewed in this report. In resectable NSCLC, the results of two small trials have yielded positive trends in favor of neoadjuvant chemotherapy. However, neither of these trials was flawless; therefore, firm conclusions cannot yet be drawn. In selected patients with initially nonresectable NSCLC, several phase II studies have demonstrated the potential utility of induction chemotherapy or combined chemoradiation therapy. A relatively high proportion of these patients were rendered resectable. Pathologic complete remissions were observed in up to 25% of patients and survival rates improved significantly, particularly in patients achieving pathologic complete remission. A current intergroup trial will ultimately assess the utility of surgery after induction chemoradiation in this group of patients. The advent of newer agents with demonstrated activity in advanced NSCLC has led to the design of potentially more effective but also more toxic neoadjuvant regimens. Some of these are under investigation in large randomized phase III trials, which should ultimately elucidate the role of induction therapy with "modern" agents in potentially curable NSCLC.

Antineoplastic Agents↗