Neoadjuvant radiotherapy concurrent with weekly paclitaxel and carboplatin and followed by surgery in locally advanced non-small-cell lung cancer

Thirty-seven patients were enrolled in a phase II study to evaluate the efficacy and toxicity of neoadjuvant radiotherapy concurrent with weekly paclitaxel and carboplatin in locoregionally advanced non-small-cell lung cancer (NSCLC). The study was also designed to evaluate the operability following concurrent chemoirradiation. The following response rates to chemoirradiation were obtained: complete response (CR) 5 of 37 (13.5%), partial response 14 of 37 (38%), stable disease 12 of 37 (32.5%) and PD 6 of 37 (16%). Twenty patients underwent surgery, and in 19 patients the tumor was totally resected. There was pathologic CR in 4 patients. Moderate/severe esophagitis developed in 16 patients (43%); hematologic toxicity was mild. There was one case of postoperative mortality. Nine patients are alive without evidence of disease at 5+ to 39+ months. Median survival is 22 months. It is concluded that neoadjuvant radiotherapy concurrent with weekly paclitaxel/carboplatin is effective and well tolerated in patients and feasible for patients with locally advanced NSCLC, allowing complete tumor resection in 56% of the cases.     

Induction chemotherapy plus high-dose radiotherapy versus radiotherapy alone in locally advanced unresectable non-small-cell lung cancer

Background: High-dose radiation therapy is generally recommendedas standard treatment in regionally advanced unresectable non-small-celllung cancer (NSCLC), but medianand long-term survival remainpoor. Some reports have recently shown an improvement of resultsin advanced NSCLC when cisplatin was included in the chemotherapyregimens. Therefore, we designed a randomized trial to determinewhether induction chemotherapy before high-dose radiotherapyimproves response rate and survival in stage HI NSCLC over thatachieved with radiotherapy alone. Patients and methods: From March, 1984 to December, 1988, 66consecutive patients with stage HI unresectable NSCLC were randomizedto one of two treatment arms; 61 were evaluable for survivaland 58 for response and toxicity. Patients randomly assignedto arm A received cisplatin (CDDP 100 mg/m² on day 1) and etoposide(VP 16 120 mg/ m² on days 1, 2, 3) every 3 wks for 3 coursesfollowed by radiotherapy 56 Gy on pre-treatment tumor volumeand 40 Gy on mediastinum and bilateral supraclavicular nodes.Patients assigned to arm B received only the same radiotherapy.The 61 eligible patients were comparable in terms of age, performancestatus, histology and treatment. Results: Response rate was 53% in arm A and 32% in arm B. Themedian survival was 52 wks for the combined treatment arm and36 wks for the radiation therapy arm. At six years of follow-upall the patients were dead. Toxicity was mild and no treatment-relateddeaths were recorded. Conclusion: Induction chemotherapy produced a better responserate and a trend of improved survival (4 months) but a significantsurvival advantage was not achieved (p < 0.11), probablybecause of the small number of patients enrolled in the trial. chemotherapy, non-small-cell lung cancer, radiotherapy, combined treatment     

Induction chemotherapy with carboplatin-paclitaxel followed by standard radiotherapy with concurrent daily low-dose cisplatin plus weekly paclitaxel for inoperable non-small-cell lung cancer

Both induction chemotherapy and concurrent platinating agents have been shown to improve results of thoracic irradiation in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This phase II study investigated activity and feasibility of a novel chemoradiation regimen, including platinum and paclitaxel, both as induction chemotherapy and concurrently with thoracic radiotherapy. Previously untreated patients with histologically/cytologically proven unresectable stage I-III NSCLC were eligible. Induction chemotherapy consisted of 2 courses of 200 mg/m2 paclitaxel and carboplatin at AUC of 6 mg/mL/min every 3 weeks. From day 43, continuous thoracic irradiation (60 Gy in 30 fractions radiotherapy for 6 weeks) was given concurrently with daily cisplatin at a dose of 5 mg/m2 intravenously and weekly paclitaxel at a dose of 45 mg/m2 for 6 weeks. Fifteen patients were accrued in the first stage of the trial. According to the previous statistical considerations, accrual at the second stage of the study was halted as a result of the achievement an insufficient number of successes. Major toxicity of combined chemoradiation was grade III-IV esophagitis requiring hospitalization for artificial nutrition, which occurred in 58% of patients. Other toxicities included grade II-IV fatigue in 75% of patients and grade I-IV neuromuscular toxicity in 67%. Only 7 patients completed the treatment program as scheduled. Eight patients (53.3%; 95% confidence interval, 26.5-78.7%) had a major response (5 partial response, 3 complete response), 2 patients had disease progression, and 1 was stable at the end of treatment. Four patients died early. With a median follow up of 38 months, the median survival was 12 months. A combined chemoradiation program, including platinum and paclitaxel, appears difficult to deliver at full dose as a result of toxicity, mainly esophagitis. More active and less toxic combined modality treatments need to be developed for inoperable NSCLC.     

Induction platinum-based chemotherapy followed by radical hyperfractionated radiotherapy with concurrent chemotherapy in the treatment of locally advanced non-small-cell carcinoma of the lung

This study evaluated tolerance, local control, and short-term survival in patients with locally advanced non-small-cell lung carcinoma treated with induction chemotherapy followed by radical hyperfractionated radiotherapy with concurrent chemotherapy. Thirty-one patients with stage IIIa (N2) or IIIb tumors were treated with cis-platinum-based induction chemotherapy for 1 to 4 courses followed by radical hyperfractionated radiotherapy (69.6 Gy) with concurrent chemotherapy given at the beginning and end of radiotherapy. Induction chemotherapy produced no complete responses and 18 (58%) partial responses. After completion of radiotherapy, 4 patients had complete response (13%) and 23 patients (74%) partial response. The patterns of failure were as follows: intrathoracic, 6 patients (22%); intrathoracic + distant metastasis, 6 patients (22%); distant metastasis without thoracic failure, 5 patients (19%). Six patients of the 12 with intrathoracic failure experienced in-field radiotherapy pure local failure. At the time of this analysis, 10 patients were alive and well (4 complete and 6 partial responders). Actuarial survival projected at 39 months is 35%. No benefit was observed for those patients responding to induction chemotherapy. Toxicity was as follows: grade III neutropenic fever in 4 patients (13%), grade IV neutropenia in 13 patients (42%), pneumonia in 6 patients (19%), grade III esophagitis in 4 patients (13%) and severe clinical pneumonitis in 1 patient (3%). Induction chemotherapy followed by chemoradiotherapy is feasible, and the preliminary results are encouraging. Complete response after radiotherapy appeared to be related to short-term disease-free survival, and decisions based on the response to chemotherapy may be equivocal.     

Induction chemotherapy followed by concurrent standard radiotherapy and daily low-dose cisplatin in locally advanced non-small-cell lung cancer.

Both induction chemotherapy and concurrent low-dose cisplatin have been shown to improve results of thoracic irradiation in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This phase II study was designed to investigate activity and feasibility of a novel chemoradiation regimen consisting of induction chemotherapy followed by standard radiotherapy and concurrent daily low-dose cisplatin. Previously untreated patients with histologically/cytologically proven unresectable stage IIIA/B NSCLC were eligible. Induction chemotherapy consisted of vinblastine 5 mg m(-2) intravenously (i.v.) on days 1, 8, 15, 22 and 29, and cisplatin 100 mg m(-2) i.v. on days 1 and 22 followed by continuous radiotherapy (60 Gy in 30 fractions) given concurrently with daily cisplatin at a dose of 5 mg m(-2) i.v. Thirty-two patients were enrolled. Major toxicity during induction chemotherapy was haematological: grade III-IV leukopenia was observed in 31% and grade II anaemia in 16% of the patients. The most common severe toxicity during concurrent chemoradiation consisted of grade III leukopenia (21% of the patients); grade III oesophagitis occurred in only two patients and pulmonary toxicity in one patient who died of this complication. Eighteen of 32 patients (56%, 95% CI 38-73%) had a major response (11 partial response, seven complete response). With a median follow-up of 38.4 months, the median survival was 12.5 months and the actuarial survival rates at 1, 2 and 3 years were 52%, 26% and 19% respectively. The median event-free survival was 8.3 months with a probability of 40%, 23% and 20% at 1, 2 and 3 years respectively. Induction chemotherapy followed by concurrent daily low-dose cisplatin and thoracic irradiation, in patients with locally advanced NSCLC, is active and feasible with minimal non-haematological toxicity. Long-term survival results are promising and appear to be similar to those of more toxic chemoradiation regimens, warranting further testing of this novel chemoradiation strategy.     

Induction chemotherapy with paclitaxel plus carboplatin followed by paclitaxel with concurrent radiotherapy in stage IIIB non-small-cell lung cancer (NSCLC) patients: a phase II trial

PURPOSE: We conducted a prospective phase II trial to evaluate the efficacy and toxicity of induction chemotherapy with paclitaxel plus carboplatin followed by concurrent radiotherapy with weekly paclitaxel in stage IIIB non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Patients with stage IIIB NSCLC received two 3-week cycles of paclitaxel 200mg/m(2) combined with carboplatin (target area under the plasma concentration curve (AUC) of 6 mg/ml) followed by weekly paclitaxel 50mg/m(2) concurrently with radiotherapy consisted of 2 Gy daily, 5 days per week (60 Gy total dose in 6 weeks). The median follow-up period was 5 years. RESULTS: Between March 1999 and January 2002, 21 patients were enrolled and analyzed. Ninety percent of patients completed the planned treatment schedule. The overall response rate was 76% (24% complete response and 52% partial response). The median overall survival time was 15 months and the 1-year, 2-year and 5-year overall survival rates were 57, 33 and 24%, respectively. The disease progression rate at 1 year was 43% and the median progression-free survival was 8 months. During the chemoradiation period, grade 3-4 oesophagitis and pneumonitis were observed in 24 and 14% of patients, respectively. CONCLUSIONS: Induction chemotherapy with carboplatin and paclitaxel followed by weekly paclitaxel with concurrent radiotherapy was found to be active and tolerable in selected stage IIIB NSCLC patients. Further studies are needed to improve the safety profile and outcome in this setting.     

Induction chemotherapy with albumin-bound paclitaxel plus lobaplatin followed by concurrent radiochemotherapy for locally advanced esophageal cancer

BACKGROUNDAlbumin-bound paclitaxel (ABP) has been used as second- and higher-line treatments for advanced esophageal cancer, and its efficacy and safety have been well demonstrated. Lobaplatin (LBP) is a third-generation platinum antitumor agent; compared with the first two generations of platinum agents, it has lower toxicity and has been approved for the treatment of breast cancer, small cell lung cancer, and chronic granulocytic leukemia. However, its role in the treatment of esophageal cancer warrants further investigations.AIMTo investigate the efficacy and safety of induction chemotherapy with ABP plus LBP followed by concurrent radiochemotherapy (RCT) for locally advanced esophageal cancer. METHODSPatients with pathologically confirmed advanced esophageal squamous cell carcinoma (ESCC) at our hospital were enrolled in this study. All patients were treated with two cycles of induction chemotherapy with ABP plus LBP followed by concurrent RCT: ABP 250 mg/m², ivgtt, 30 min, d1, every 3 wk; and LBP, 30 mg/m², ivgtt, 2 h, d1, every 3 wk. A total of four cycles were scheduled. The dose of the concurrent radiotherapy was 56-60 Gy/28-30 fractions, 1.8-2.0 Gy/fraction, and 5 fractions/wk.RESULTSA total of 29 patients were included, and 26 of them completed the treatment protocol. After the induction chemotherapy, the objective response rate (ORR) was 61.54%, the disease control rate (DCR) was 88.46%, and the progressive disease (PD) rate was 11.54%; after the concurrent RCT, the ORR was 76.92%, the DCR was 88.46%, and the PD rate was 11.54%. The median progression-free survival was 11.1 mo and the median overall survival was 15.83 mo. Cox multivariate analysis revealed that two cycles of induction chemotherapy followed by concurrent RCT significantly reduced the risk of PD compared with two cycles of chemotherapy alone (P = 0.0024). Non-hematologic toxicities were tolerable, and the only grade 3 non-hematologic toxicity was radiation-induced esophagitis (13.79%). The main hematologic toxicity was neutropenia, and no grade 4 adverse event occurred. CONCLUSIONInduction chemotherapy with ABP plus LBP followed by concurrent RCT is effective in patients with locally advanced ESCC, with mild adverse effects. Thus, this protocol is worthy of clinical promotion and application.     

Induction paclitaxel/carboplatin followed by concurrent chemoradiation therapy for unresectable stage III non-small-cell lung cancer: a limited-access study--CALGB 9534

BACKGROUND: This phase II cooperative group study of patients with unresectable stage III non-small-cell lung cancer was designed to treat patients with induction chemotherapy with paclitaxel and carboplatin (PC) followed by concurrent chemotherapy with the same chemotherapy plus thoracic irradiation to 66 Gy. PATIENTS AND METHODS: All enrolled patients were scheduled to receive 2 cycles of induction PC at conventional doses. All nonprogressing patients were subsequently treated with concurrent chemoradiation, including 7 weekly doses of PC and once-daily thoracic irradiation. The eligibility criteria allowed treatment of an expanded population of patients, unrestricted by previous weight loss. RESULTS: Despite the fact that 22% of patients had experienced > 5% weight loss in the preceding 6 months, 23 of the 40 eligible patients (58%) responded to the overall regimen. A 3-year failure-free survival rate of 15% and a 3-year overall survival rate of 27% were achieved. The 3-year overall survival rate is consistent with landmark cooperative group results for the combined modality treatment of a more highly selected patient population. CONCLUSION: The feasibility of this therapeutic approach in a cooperative group setting and inclusive of patients who were representative of the general population of stage III lung cancer patients was established.     

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.     

A phase II trial of preoperative concurrent radiation therapy and weekly paclitaxel/carboplatin for patients with locally advanced non-small-cell lung cancer

This study was designed to evaluate the efficacy and toxicity of a novel preoperative combined-modality regimen in patients with locally advanced non-small-cell lung cancer (NSCLC). Patients with clinical stage IIB, IIIA, or IIIB NSCLC received preoperative combined-modality therapy with concurrent radiation therapy (RT) and weekly paclitaxel/carboplatin for 5 consecutive weeks. After this treatment, patients believed to have resectable disease by standard surgical criteria underwent thoracotomy. Patients whose disease remained unresectable after initial therapy received further RT with concurrent paclitaxel/carboplatin. Of 107 patients entered into this clinical trial, only 20 patients (19%) were considered to have surgically resectable disease at the time of study entry. Ninety-eight patients (92%) completed preoperative combined-modality therapy. Forty-nine patients (46%) underwent thoracotomy and 34 patients had definitive resection. Fourteen patients (13%) had pathologic complete response (pCR). Thirteen of 18 patients (72%) with clinical stage T3 N0 (IIB) tumors had definitive resections, and 33% had pCR. After a median follow-up of 32 months, the 1- and 2-year actuarial survival rates for the entire group are 64% and 42%, respectively. Favorable-prognosis subgroups included patients who had definitive resection and patients with clinical stage T3 N0 tumors (2-year survival rates of 67% for both subgroups). Preoperative therapy with RT and weekly paclitaxel/carboplatin showed activity in this patient population; however, disease in the majority of patients with extensive involvement of mediastinal nodes remained unresectable after this treatment. Results in patients who initially had unresectable disease do not appear different than results achieved with concurrent RT/chemotherapy approaches. Postoperative complications associated with this preoperative combined-modality regimen were more frequent than expected with resection alone.     

Safety and efficacy of sequential chemotherapy with carboplatin plus gemcitabine followed by weekly paclitaxel in advanced non-small cell lung cancer

Background

Improving survival in non-small cell lung cancer (NSCLC) will require new strategies or new drugs. Sequential administration of conventional non-cross-resistant cytotoxic drugs offers an opportunity to increase drug diversity while maintaining dose intensity. This Phase II trial was designed to assess the efficacy and feasibility of such a regimen in advanced NSCLC.

Methods

Patients with NSCLC stage IIIB or IV received as first-line treatment four cycles of carboplatin (AUC 5) (day 1) plus gemcitabine 1000 mg/m² (days 1 and 8) every 3 weeks. Thereafter, treatment continued with 12 weekly cycles of paclitaxel 80 mg/m².

Results

In total, 46 patients were included. Median age was 59.6 years (range 41.3–74.3 years) and 93.5 % (n = 43) had Eastern Cooperative Oncology Group performance score of 0 or 1. All but 6 had stage IV disease, and 13 (28.3 %) had squamous cell carcinomas. Thirty-six (78 %) patients completed 4 cycles of carboplatin–gemcitabine and 35 patients received at least 1 cycle of paclitaxel, of whom 16 (46 % of total) patients completed 12 cycles of paclitaxel. The overall objective response rate was 49 %. Sixteen (37 %) patients had a response to carboplatin–gemcitabine, increasing to 21 (49 %) patients after administration of paclitaxel. Of the 13 assessable patients who showed a partial response (PR) on carboplatin–gemcitabine, 12 (92 %) patients showed also a PR on paclitaxel. Of 19 assessable patients with stable disease (SD) on carboplatin–gemcitabine, 4 (21 %) had a PR and 13 (68 %) SD on paclitaxel. Toxicity was moderate: 24 % stopped because of toxicity.

Conclusion

Sequential chemotherapy with carboplatin–gemcitabine and weekly paclitaxel is active and feasible in advanced NSCLC patients.     

Daily low-dose cisplatin plus concurrent high-dose thoracic radiotherapy in elderly patients with locally advanced unresectable non-small-cell lung cancer

There are few prospective studies of concurrent chemoradiotherapy in elderly patients with locally advanced unresectable non-small-cell lung cancer (NSCLC), although the therapy has proved superior to radiotherapy alone for the treatment of younger patients. We conducted a pilot study to assess the tolerance and efficacy of concurrent cisplatin and thoracic radiation in elderly patients with locally advanced unresectable NSCLC. Eligible patients were more than 71 years old and had unresectable Stage I, II, or III NSCLC. Cisplatin was administered at 6 mg/m2 daily intravenously on days 1 through 5, days 8 through 12, days 29 through 33 and days 36 through 40. Beginning day on 1, thoracic radiation was delivered at 2.0 Gy daily to a total dose of 60 Gy. Twelve patients were registered and 11 were eligible. Patient characteristics were ages of 73 to 80 years, and stage III A (18%) and stage III B (73%) NSCLC. The most common grade 3 toxicities included leukopenia (20%) and thrombocytopenia (9%). Grades 3/4 elevation of serum creatinin, esophagitis and pneumonitis did not occur. The overall confirmed response rate was 82%, and median overall survival was 23 months. The 2-year survival rate was 53%. This chemoradiotherapy regimen is well tolerated with promising response and survival in elderly patients with unresectable NSCLC.     

Induction chemotherapy with carboplatin/paclitaxel followed by surgery or standard radiotherapy and concurrent daily low-dose cisplatin for locally advanced non-small cell lung cancer (NSCLC)

Five-year survival in patients with unresectable non-small-cell lung cancer (NSCLC) is less than 10%. In the present phase II study, 43 patients with locally advanced stage IIIA or selected IIIB NSCLC were given four courses of carboplatin AUC = 6 and paclitaxel 200 mg/m2 (3-hour infusion), every 3 weeks. Responsive patients, when possible, underwent surgery followed by standard radiotherapy (50 Gy) or radiotherapy (60 Gy), with concurrent cisplatin as intravenous continuous infusion of 4 mg/m2/d. Sixteen of the 42 evaluable patients achieved partial response (38%) and 3 complete response (CR) (7%) for an overall response rate of 45% (95% CI 30.1-60.2). R0 resectability rate was 29%, with 21% of pathologic CRs. Three more CRs were achieved with concurrent chemoradiotherapy in responsive but unresected patients. Grade III/IV hematologic toxicity was 9%, while one perioperative death occurred. The median duration of response was 14 months (range: 3-44+); median survival was 15 months (range: 9-47+). One-year and 2-year survival rates were 51% and 22%, respectively. The median survival in the responsive resected patients was 26 months, with 2-year survival of 57%. Carboplatin/paclitaxel represents an effective and well-tolerated induction therapy, suggesting its possible role in combination with radiotherapy as neoadjuvant treatment in locally advanced NSCLC in alternative to cisplatin-based regimens.     

A phase II trial of induction chemotherapy followed by continuous hyperfractionated accelerated radiotherapy in locally advanced non-small-cell lung cancer

Background and purpose

We conducted a phase II study combining induction chemotherapy with continuous hyperfractionated accelerated radiotherapy (CHART) in locally advanced non-small-cell lung cancer (NSCLC).

Materials and methods

A total of 40 patients with stage III NSCLC were enrolled. All patients received 3 cycles of chemotherapy followed by CHART (56 Gy in 36 fractions over 12 days). The primary outcome measure was radiation toxicity. Secondary endpoints were response rate, overall survival, disease-free survival and loco-regional progression-free survival.

Results

Acute radiation toxicity was minimal and there were no significant late toxicities. The response rate after completion of chemoradiation was 65%. The median and 2-year overall survival, progression-free survival and loco-regional progression-free survivals were 15.7 months, 28%; 12.1 months, 23%; and 26.4 months, 51%, respectively.

Conclusions

Induction chemotherapy can be safely combined with CHART. The survival results are consistent with previous studies of chemotherapy followed by accelerated radiotherapy. This approach should be compared with synchronous chemoradiation to determine if it represents a less toxic alternative.     

Phase II study of concurrent thoracic radiotherapy in combination with weekly paclitaxel plus carboplatin in locally advanced non-small cell lung cancer: LOGIK0401

Objectives

Concurrent chemoradiotherapy for regionally advanced stage III non-small cell lung cancer is the standard treatment method. However, the clinical implications of consolidation chemotherapy following chemoradiation have been unclear. Therefore, we conducted a phase II study of concurrent weekly carboplatin plus paclitaxel treatment in combination with radiotherapy followed by vinorelbine monotherapy. The primary endpoint was the 1-year survival rate.

Patients and methods

Chemonaive PS 0–1 patients with stage IIIA/B NSCLC were enrolled. During the concurrent chemoradiation phase, patients were treated with weekly paclitaxel 40 mg/m² plus carboplatin AUC 2. The primary tumor and involved nodes received 60 Gy in 2-Gy fractions over 6 weeks. During the consolidation phase, vinorelbine 25 mg/m² on days 1 and 8 was repeated for three cycles.

Results

A total of 40 eligible patients (72.5 % male; median age, 63 years; range 29–74 years) were analyzed for efficacy. Squamous cell carcinoma was the most common histology (47.5 %), and more patients had clinical stage IIIB (55 %) cancer. The average radiation dose was 56.5 Gy, and the average number of carboplatin plus paclitaxel cycles was 4.93. Seventeen patients proceeded to the consolidation chemotherapy phase, and 14 completed three cycles of vinorelbine monotherapy. The objective response rate was 75.0 %, including 1 patient who achieved a complete response. Progression-free survival and overall survival (OS) were 46 weeks [95 % confidence interval (CI) 31–64 weeks] and 110 weeks (95 % CI 90–184 weeks), respectively. The OS rate at 1 and 2 years was 85.0 % (95 % CI 69.6–93.0 %) and 53.9 % (95 % CI 37.1–68.0 %), respectively.

Conclusion

Concurrent chemoradiation with weekly carboplatin and paclitaxel followed by vinorelbine consolidation is effective for stage III non-small cell lung cancer and shows a generally mild toxicity profile.     

Weekly paclitaxel with concurrent radiotherapy followed by adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma

Purpose

To evaluate the efficacy and toxicity of weekly paclitaxel with concurrent radiotherapy followed by adjuvant chemotherapy (AC) in patients with locally advanced nasopharyngeal carcinoma (NPC).

Methods and materials

Between 2004 and 2007, 54 patients with locally advanced NPC were included in this protocol. Patient characteristics: median age 48; 69% male; 52% World Health Organization (WHO) III; 50% stage III, 50% stage IV. The patients underwent a course of definitive conventional radiotherapy (70 Gy in 7 weeks with 2 Gy/fraction), with concurrent weekly paclitaxel 35 mg/m² from the first to the sixth week of radiation. AC was started 4 weeks after the end of the radiotherapy (RT), paclitaxel 135 mg/m² on day 1 and cisplatin 30 mg/m² on days 1-3 were administered every 4 weeks for two cycles.

Results

Median follow-up was 32 months. Eighty-five percentage of complete response and 15% partial response were achieved at the time of one month after AC. The 3-year actuarial rate of local regional control was 86%; distant metastases-free survival, progression-free survival and overall survival at 3 years were 81%, 69% and 76%, respectively. Forty-nine (91%) patients completed six courses of concurrent chemotherapy with weekly paclitaxel, and 4 (7%) patients delayed at the second cycle of AC. No patient developed severe acute toxicities.

Conclusions

Weekly paclitaxel with concurrent RT followed by AC is a potentially effective and toxicity tolerable method for locally advanced NPC. Further studies are needed to identify the optimal dose of weekly paclitaxel in this strategy.     

长春瑞滨和卡铂联合同步放疗治疗晚期非小细胞肺癌观察

目的：评价国产长春瑞滨(盖诺)和卡铂联合同步放疗治疗晚期非小细胞肺癌的疗效及毒副反应。方法：106例Ⅲ期NSCLC患，分为二组，化放组在放疗的同时及放疗后进行4周期化疗，化疗用药盖诺25mg／m^2在每个周期的第1、8天静脉滴注给予；卡铂300mg／m^2第1天静脉滴注。单放组行单纯放疗。结果：化放组有效率71．4％，单放组有效率为42．0％。化放组的有效率明显高于单放组(P=0．008)。化放组和单放组的1、2年生存率分别为77．39％、30．33％和58．65％、15．75％，中位生存时间分别为18个月和13个月，其差异有显性(P=0．0407)。结论：盖诺和卡铂联合同步放疗是治疗晚期非小细胞肺癌的安全有效的治疗方法，值得进一步临床研究。     

诱导化疗加三维适形放疗同步化疗不可手术的局部晚期非小细胞肺癌的疗效分析

目的 探讨诱导化疗+三维适形放疗(3DCRT)联合顺铂单药(每周方案)同步化疗不可手术的局部晚期非小细胞肺癌(NSCLC)的疗效和毒副反应.方法 76例局部晚期NSCLC患者(ⅢA期42例,ⅢB期34例)先接受2个周期的诱导化疗,再行3DCRT(DT 64～74 Gy,中位68 Gy)+同步顺铂(25 mg/m2,每周1次,共6～7周)化疗.结果 诱导化疗后2例达CR,32例达PR,有效(CR+PR)率为45%.同步化放疗后8例达CR,47例达PR,有效率为72%.全组中位生存期和中位无进展生存期分别为16.6个月和10.3个月,1、2、3年总生存率和无进展生存率分别为67%、35%、21%和42%、15%、6%.ⅢA期和ⅢB期的中位生存期、中位无进展生存期分别为19.7个月和15.6个月、10.8个月和9.4个月.主要的毒副反应为放射性食管炎、放射性肺炎、恶心呕吐和白细胞减少.治疗后45例肿瘤局部复发或(和)远处转移,其中4例照射野内复发,3例癌性胸水,38例远处转移.结论 诱导化疗后3DCRT+顺铂单药同步化放疗不可手术的局部晚期NSCLC的疗效和耐受性较好,可进一步研究.     

Twice-weekly paclitaxel and weekly carboplatin with concurrent thoracic radiation followed by carboplatin/paclitaxel consolidation for stage III non-small-cell lung cancer: a California Cancer Consortium phase II trial.

PURPOSE: Recent studies have suggested the superiority of concurrent chemoradiotherapy and the efficacy of paclitaxel/carboplatin in advanced non-small-cell lung cancer (NSCLC). In view of those results, we sought to examine the safety and efficacy of administration of radiosensitizing paclitaxel twice weekly and carboplatin weekly with concurrent thoracic radiation therapy (XRT) followed by consolidation paclitaxel and carboplatin for stage III NSCLC in a multi-institutional phase II trial. PATIENTS AND METHODS: Induction chemoradiotherapy consisted of paclitaxel 30 mg/m2 delivered intravenously (IV) for 1 hour twice weekly for 6 weeks, carboplatin at a dose based on an area under the concentration-time curve (AUC) of 1.5 mg/mL x min, given IV once weekly for 6 weeks, and concomitant XRT of 1.8 to 2.0 Gy daily for a total of 61 Gy. Patients who achieved a complete response, partial response, or stable disease received two 21-day cycles of consolidation chemotherapy consisting of paclitaxel 200 mg/m2 IV for 3 hours and carboplatin at a dose based on an AUC of 6 mg/mL x min. RESULTS: Thirty-four patients were eligible. Their median age was 62 years (range, 39 to 73 years), 59% were female, 41% were male, 94% had a performance status of 0 or 1, 38% had stage IIIA NSCLC, and 62% had stage IIIB NSCLC. Common grade III and IV toxicities during the induction chemoradiation phase included esophagitis (38%) and neutropenia (12%). The most common adverse reaction during consolidation chemotherapy was grade III neutropenia in five patients (15%). The overall response rate was 71%, which was achieved in the induction phase. The median follow-up was 20 months, the median survival was 17 months, and 2-year actuarial survival rate was 40% (95% confidence interval, 20% to 65%). CONCLUSION: This regimen is tolerable and results are promising. We recommend further evaluation of this regimen in a phase III trial.     

Phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer

We conducted a phase II trial to investigate the efficacy of concurrent chemoradiation in patients with stage III non-small-cell lung cancer (NSCLC). Thirty patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Patients received six weekly cycles of paclitaxel 45 mg/m(2) over 1 h; carboplatin at (area under the curve) AUC 2; and radiation therapy of 60 Gy. Radiation was administered to the primary tumor and regional lymph nodes (40 Gy over 4 weeks) followed by a boost to the primary tumor (20 Gy in 2 weeks). After the initial phase of concurrent chemoradiation, patients received an additional four cycles of paclitaxel 175 mg/m(2) over 3 h and carboplatin at AUC 6 every 3 weeks. The overall objective response rate of 30 assessable patients was 76.7%. At the median follow-up time of 13.1 months, the median survival time was 14.5 months (95% CI, 10.59-18.48). The median progression-free survival was 10.5 months (95% CI, 7.72-13.28). The major toxicity was hematologic. The incidence of grade 3 esophagitis was 10%. In conclusion, this chemoradiation regimen is well tolerated and shows significant clinical results for locally advanced NSCLC. Locoregional failure rate remains an important issue with this newer chemotherapeutic regimen. A novel chemotherapy and radiation therapy is clearly needed.