Phase II study with fractionated schedule of docetaxel and cisplatin in patients with advanced non-small cell lung cancer

Background

Docetaxel and cisplatin combination chemotherapy is established first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). We evaluated a weekly schedule of docetaxel and cisplatin for efficacy and tolerability in patients with chemotherapy-naive NSCLC.

Methods

Patients enrolled in this study had stage IIIB or IV NSCLC with measurable disease, no prior chemotherapy, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. Treatment consisted of docetaxel 40 mg/m² and cisplatin 35 mg/m² given on D1 and D8 every 3 weeks. Patients were evaluated for response after every 2 cycles of treatment.

Results

Thirty six patients were enrolled, and 35 underwent treatment. Of these, 29 were males and 7 females, median age was 61 years (range, 38–68). About 31 patients had ECOG PS 0-1 and 4 patients had ECOG PS 2. Fifty seven percentage (20/35) of patients had adenocarcinoma and 74.3% (26/35) had stage IV disease. A total of 153 cycles of chemotherapy were administered. Of the 35 patients treated, 17 (48.6%) achieved partial response, 11 (31.4%) showed stable disease, and 6 (17.1%) had progressive disease. Median duration of response was 5.3 months (95% CI: 4.2–6.2 months), and median time to disease progression was 4.6 months (95% CI: 2.9–6.3 months). Estimated overall survival at 1 year was 65.7%. The major hematologic toxicity was myelosuppression. Grade 3 or 4 anemia occurred in 6 cycles, and grade 3 or 4 neutropenia was observed in four cycles. Major non-hematologic toxicities were grade 3 nausea in three patients and grade 3 fatigue in two patients. Three patients developed pneumonia and one patient had infectious colitis. There were no treatment-related deaths in this study.

Conclusions

Weekly schedule of docetaxel and cisplatin as first-line treatment for NSCLC had good efficacy and manageable toxicity.     

Clinical analysis of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer

Objective

The purpose of this study was to assess the curative effect and adverse reaction of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer (NSCLC).

Methods

This prospective randomized controlled trial included 115 patients with locally advanced NSCLC were randomly divided into experimental and control groups and were treated from January 2007 to January 2010. The experimental group of 63 cases was treated with two cycles of induction chemotherapy before operation, radical surgery had been performed about three weeks after completion of chemotherapy, followed by received two cycles of chemotherapy. And the control group (52 cases) was treated at first with radical surgery, then treated with four cycles of chemotherapy. Two groups of the cases received routine thoracic radiotherapy with a total dose of 45 Gy. One cycle of gemcitabine combined with cisplatin regimen included gemcitabine 1000 mg/m² on day 1 and day 8 and cisplatin 25 mg/m² on day 1, day 2 and day 3 by intravenous infusion, with 21 days as one cycle. The tumor recurrence was evaluated by chest CT and abdominal B-ultrasound. Efficacy and toxicity results were compared by two groups.

Results

All patients were followed up for three months to two years. The surgical stage of the experimental group reduced, two-years disease-free survival and postoperative recovery in the experimental group were better than in the control group, the difference was statistical significant. Toxicity and side effect after chemotherapy were mainly bone marrow suppression and gastrointestinal reactions, other complications included thrombocytopenia, leukopenia, anemia, liver and kidney dysfunction were no significant difference in two groups.

Conclusion

Preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced lung cancer can reduce the surgical staging and extend the postoperative disease-free survival.     

Docetaxel-based induction therapy prior to radiotherapy with or without docetaxel for non-small-cell lung cancer

This trial aimed to assess the feasibility and tumour control of concurrent chemoradiotherapy or radiotherapy alone after docetaxel-based induction chemotherapy in locally advanced non-small-cell lung cancer (NSCLC). Patients with stage IIIA/IIIB NSCLC received two 21-day cycles of induction chemotherapy with docetaxel (85 mg m(-2), day 1) plus cisplatin (40 mg m(-2), days 1 and 2). Patients without disease progression on day 43 were randomised to radiotherapy (2 Gy for 5 days week(-1); total 60 Gy) alone or with docetaxel 20 mg m(-2) once weekly every 6 weeks. Of 108 patients who received induction chemotherapy, 104 were evaluable for response. After induction chemotherapy, the overall response rate (ORR) was 44%; 91 (88%) patients had no disease progression and 89 were subsequently randomised to local treatment. After randomised therapy, the ORR was 53% (chemoradiotherapy 58%; radiotherapy 48%). Median survival and time to progression were 14.9 and 7.8 months, respectively, for chemoradiotherapy and 14.0 and 7.5 months, respectively, for radiotherapy. The most common toxicities during induction chemotherapy and randomised therapy were grades 3-4 neutropenia and grade 3 lymphocytopenia, respectively. Docetaxel-cisplatin induction therapy followed by concurrent docetaxel and thoracic radiotherapy is a feasible treatment option, showing good clinical activity and tolerability, for locally advanced NSCLC.     

Multicenter phase II study evaluating docetaxel and cisplatin as neoadjuvant induction regimen prior to surgery or radiochemotherapy with docetaxel,followed by adjuvant docetaxel therapy in chemonaive patients with NSCLC stage II,IIIA and IIIB (TAX-AT 1.203 Trial)

Objectives

Neoadjuvant therapy with a platinum based doublet is an option in NSCLC patients with upfront resectable disease. However, the role of neoadjuvant induction in stages IIIA and IIIB and in initially not resectable patients is unclear.

Patients and methods

In this phase II trial, 78 patients with locally advanced NSCLC, of whom 56 were considered not resectable at initial diagnosis, were treated with three neoadjuvant cycles of docetaxel and cisplatin and subjected to radical surgery if resectable. Definitive radiochemotherapy (RCT) using weekly docetaxel was the prespecified alternative if patients were not resectable at restaging. The primary objective was response to neoadjuvant induction.

Results

After induction, 36 (46%) were radically operated and 24 (31%) were treated with RCT. Overall, 32 patients (41%) completed the entire study plan. Partial response to induction therapy was observed in 43 patients (55%); furthermore, 19 of 56 initially not resectable cases (34%) became resectable upon induction. Median progression-free (PFS) and overall survival (OS) were 8.5 and 16.4 months for the whole cohort. Encouragingly, conversion to resectability was predictive for favorable outcome. On the other hand, patients who were not resectable at restaging and received RCT were characterized by a rather unfavorable prognosis (5-year and 10-year OS, whole cohort: 20% and 12%; RCT: 8% and 0%; surgery: 37% and 24%, respectively).

Conclusion

Neoadjuvant induction with the doublet docetaxel/cisplatin and subsequent radical resection resulted in favorable survival. Of note, conversion to resectability was mandatory for the chance of cure in patients considered initially not resectable.     

Weekly docetaxel and cisplatin with concomitant radiotherapy in addition to surgery and/or consolidation chemotherapy in stage III non-small cell lung cancer

Purpose  

The aim of this study was to evaluate efficacy and feasibility of a combination of weekly docetaxel and cisplatin administered concomitantly with radiotherapy followed by surgery in addition to consolidation chemotherapy with docetaxel and cisplatin administered every 3 weeks in stage III non-small cell lung cancer (NSCLC).     

TPF induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma: Long term results of a Tunisian series

Purpose

We represent in this study the long term results of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by concurrent chemoradiotherapy in Tunisian patients with locally advanced nasopharyngeal carcinoma. The objective of our study is to analyse the efficacy as well as the toxicity of this therapeutic protocol.

A phase II study of concurrent chemoradiotherapy with weekly docetaxel and cisplatin in advanced oesophageal cancer

Background

Concurrent chemoradiotherapy (CRT) is a main treatment option for patients with advanced oesophageal cancer. However, improvement of survival outcomes and toxicities according to the selected treatment is still needed. This phase II trial was conducted to assess the efficacy and safety of concurrent CRT with weekly docetaxel and cisplatin in advanced oesophageal cancer.

Methods

Patients with unresectable oesophageal cancer due to advanced stage or patients medically unfit for surgery were enrolled. Patients received 20?mg/m² docetaxel and 25?mg/m² cisplatin in weeks 1, 2, 3, 5, 6, and 7 with concurrent 54-Gy radiotherapy at 200?cGy/day.

Results

Thirty-six patients with oesophageal squamous cell carcinoma were enrolled from December 2007 to December 2009. Among them, the toxicity and response rate of 35 were evaluated. Thirty-five patients completed radiotherapy as planned, and 33 completed chemotherapy as planned. Grade 3 or 4 toxicity during CRT included leucopenia (5.7?%), febrile neutropenia (2.9?%), oesophagitis (22.9?%), and tracheo-oesophageal fistula (5.7?%). After CRT, 8 patients (22.9?%) had a complete response, 22 (62.9?%) had a partial response, 4 (11.4?%) had stable disease, and 1 (2.9?%) had progressive disease. Improvement of dysphagia was observed in 85.3?%. At a median follow-up of 26.7?months, the median time to progression was 13.5?months, and median overall survival was 26.9?months. The 3-year progression-free survival rate was 16.7?%, and survival rate was 27.8?%.

Conclusion

Concurrent CRT with weekly docetaxel and cisplatin was well tolerated and is a convenient combination with promising efficacy. This result indicated favourable activity in terms of both tumour and symptom control.     

Results from a single institution phase II trial of concurrent docetaxel/carboplatin/radiotherapy followed by surgical resection and consolidation docetaxel/carboplatin in stage III non-small-cell lung cancer

Background

The optimal treatment of locally advanced non–small-cell lung cancer (NSCLC) remains controversial. We hypothesized that using a trimodality approach in selected patients with stage IIIA/IIIB disease would be both feasible and efficacious with reasonable toxicity.

Patients/Methods

We enrolled 13 patients with resectable stage III NSCLC on a prospective phase II trial of trimodality therapy. Induction treatment consisted of weekly docetaxel 20 mg/m² and weekly carboplatin at an area under curve (AUC) of 2 concurrent with 45 Gy thoracic radiotherapy. Resection was performed unless felt to be unsafe or if patients had progressive disease. Postoperative consolidation consisted of docetaxel 75 mg/m² and carboplatin at an AUC of 6 every 3 weeks for 3 cycles with growth factor support.

Results

All patients responded to induction chemoradiotherapy as measured by total gross tumor volume reductions of 43% on average (range, 27%-64%). Twelve patients underwent resection of the tumor and involved nodes, yielding a resectability rate of 92%. The primary endpoint of 2-year overall survival (OS) was 72% (95% confidence interval [CI], 36%-90%), and 2-year progression-free survival (PFS) was 36% (95% CI, 9%-64%). The maximal toxicity observed per patient was grade II in 5 patients (38%); grade III in 7 patients (54%); grade IV in 1 patient (8%); and grade V in none.

Conclusion

This trimodality approach resulted in promising outcomes with reasonable toxicity in carefully selected patients with stage III NSCLC at a single institution.     

Phase II study of docetaxel,cisplatin, and concurrent radiation followed by platinum-based adjuvant chemotherapy for technically unresectable,locally advanced head and neck squamous cell carcinoma

Background

Phase I study of weekly administration of low-dose docetaxel/cisplatin concurrent with conventionally fractionated radiotherapy for locally advanced head and neck squamous cell carcinoma suggested the recommended dose of docetaxel at 10 mg/m² and cisplatin at 20 mg/m². Phase II study of the concurrent chemoradiotherapy for technically resectable disease showed satisfactory results.

Methods

This phase II study was designed to address efficacy and safety when patients with technically unresectable disease were treated with concurrent chemoradiotherapy, followed by two cycles of moderate-dose platinum-based adjuvant chemotherapy: docetaxel, cisplatin, and fluorouracil (modified TPF). Modified TPF was replaced with docetaxel/carboplatin when renal impairment became evident. Surgical salvage was considered when residual or recurrent locoregional disease was technically resectable and free of distant metastasis.

Results

Of 33 enrolled patients, 31 were analyzable: 24 (78 %) and 18 (58 %) patients completed chemoradiotherapy and adjuvant chemotherapy, respectively; 15 (48 %) patients completed study treatment per protocol, and overall complete response rate was 45 %. Seven patients underwent surgical salvage, which was successful in 4 patients. At a median follow-up of 60.8 months for surviving patients, median progression-free survival and median overall survival were 16.2 and 39.9 months, respectively. Grade 3 or 4 toxicity included mucositis (77 %) and dysphagia (45 %) during the chemoradiotherapy period and neutropenia (100 %) and febrile neutropenia (35 %) during the adjuvant period. No patient died of toxicity.

Conclusion

The tested regimen seems effective, although there is room for improvement in adjuvant chemotherapy because of the high toxicity and low compliance of modified TPF.

     

Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer

Background

Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC).

Methods

This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy.

Results

Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8–18.2), and the median overall survival was 26.9 months (95% CI, 15.3–38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%).

Conclusions

The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings.     

Treatment adherence in concurrent chemoradiation in patients with locally advanced non-small cell lung carcinoma: Results of daily intravenous prehydration

Purpose

To test the hypothesis that daily intravenous pre-hydration decreases renal toxicity and improves chemotherapy adherence in patients receiving daily cisplatin to concurrent radiotherapy for locally advanced non-small cell lung cancer (NSCLC).

Patients and methods

Patients with locally advanced NSCLC were treated between 2008 and August 2012 with daily 6 mg/m² cisplatin as a bolus injection in 10 ml; of saline and 66 Gy/24 fr radiotherapy in 32 days. Since January 2011, the administration of cisplatin was routinely preceded by intravenous pre-hydration with 1 L of natriumchloride 0.9%. Patients were divided in a pre-hydrated (PH) and non-pre-hydrated (NPH) cohort. Serum-creatinine and glomerular filtration rate (GFR) were assessed twice weekly during treatment. Retrospectively, baseline data, toxicity, treatment adherence and efficacy data were compared.

Results

Of the 356 patients 232 NPH patients and 100 PH patients were eligible. Patient-and treatment characteristics compared equally. The median of the maximum decrease in GFR was 24% and 8% for NPH and PH (p < 0.01), respectively. Sixty-nine percent of the patients in the NPH group completed the 24 administrations of cisplatin, as compared to 83% of the PH group (p < 0.01). Nineteen percent vs. 2% of the patients in the NPH and PH group discontinued cisplatin treatment because of renal toxicity. Surprisingly, the incidence of acute esophageal toxicity grade ?2 decreased following prehydration: 62% vs. 34% (p < 0.001) for the NPH and PH groups, respectively. The one-year survival was comparable between groups (75% for NPH and 71% for PH).

Conclusion

Daily pre-hydration was associated with a reduced rate of both renal and acute esophageal toxicity and an increased chemotherapy adherence in patients receiving daily dose of cisplatin and concurrent radiotherapy for locally advanced NSCLC.     

Experience with combination of docetaxel, cisplatin plus 5-fluorouracil chemotherapy, and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma

Background

Our aim was to evaluate the efficacy and toxicity of cisplatin, fluorouracil, and docetaxel chemotherapy plus intensity-modulated radiotherapy (IMRT) for locoregionally advanced nasopharyngeal carcinoma (NPC).

Methods

Sixty patients with locoregionally advanced NPC were enrolled. Patients received IMRT plus three courses of neoadjuvant chemotherapy and two courses of adjuvant chemotherapy consisting of docetaxel (60 mg/m²/day on day 1), cisplatin (25 mg/m²/day on days 1–3), and 5-fluorouracil (500 mg/m²/day on days 1–3).

Results

The overall response rate to neoadjuvant chemotherapy was 89 %. Three months after the completion of radiotherapy, 53 (93 %) patients achieved complete regression, 3 (5 %) achieved partial response (PR), and 1 experienced liver metastasis. However, among the 3 PR patients, 2 patients had no evidence of relapse in the follow-up. With a median follow-up of 27 months (range, 6–43), the 2-year estimated locoregional failure-free survival, distant failure-free survival, progression-free survival, and overall survival were 96.6, 93.3, 89.9, and 98.3 %, respectively. Leukopenia was the main adverse effect in chemotherapy; 14 patients experienced grade 3 or grade 4 neutropenia, and 1 patient developed febrile neutropenia. The nonhematological adverse events included alopecia, nausea, vomiting, anorexia, and diarrhea. The incidence of grade 3 acute radiotherapy-related mucositis was 28.3 %; no grade 4 acute mucositis was observed. No grade 3 or grade 4 hematological toxicity occurred during radiotherapy. None of the patients had interrupted radiotherapy. The common late adverse effects included xerostomia and hearing impairment.

Conclusions

Neoadjuvant–adjuvant chemotherapy using cisplatin, fluorouracil, plus docetaxel combined with IMRT was an effective and well-tolerated alternative for advanced NPC.     

Phase I study to determine MTD of docetaxel and cisplatin with concurrent radiation therapy for stage III non-small cell lung cancer

Objective  

To evaluate the maximum tolerated dose (MTD) of docetaxel (DCT) and cisplatin (DDP) concurrently with three dimensional (3D) conformal radiotherapy or IMRT for patients with locally advanced non-small cell lung cancer (stage IIIa and IIIb) after 2–4 cycles of induction chemotherapy.     

Response to induction chemotherapy and surgery in non-organ confined bladder cancer: A single institution experience

Aim

To evaluate the outcome of patients with locally advanced muscle-invasive and/or lymph node positive bladder cancer treated with induction chemotherapy and additional surgery.

Methods

All patients who were treated with induction chemotherapy in our institution between 1990 and 2010, were retrospectively evaluated using an institutional database. Induction chemotherapy consisted of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC), or a combination of gemcitabine with either cisplatin or carboplatin (GC).

Results

In total 152 patients were identified, with a mean age of 59 years (range 31–76). One hundred and seven patients (70.4%) received MVAC, 35 patients received GC (23.0%) and 10 patients received GC after initial treatment with MVAC (6.6%). Median follow-up was 68 months (range 4–187 months). Overall 125 patients (82.2%) underwent cystectomy, whereas 12 patients (7.9%) received radiotherapy. Fifteen patients had no local treatment. Median overall survival was 18 months (95%CI 15–23 months). In 37.5% of patients with complete clinical response, residual disease was found at surgery (positive predictive value, PPV 62.5%). Complete pathological response was seen in 26.3% of patients, with a 5 year overall survival (OS) estimate of 54% (39%–74%). For patients with persisting node positive disease after induction chemotherapy and surgery OS was significantly worse (p < 0.0001).

Conclusions

Complete clinical and/or pathological response to induction chemotherapy results in a significant survival benefit. The accuracy of the current clinical response evaluation after induction chemotherapy is limited. Although surgery may be important for staging and prognostic purposes, its role is unclear in node positive disease after induction chemotherapy.     

Phase II study of cetuximab in combination with cisplatin and docetaxel in patients with untreated advanced gastric or gastro-oesophageal junction adenocarcinoma (DOCETUX study)

Background:

The conventional treatment options for advanced gastric patients remain unsatisfactory in terms of response rate, response duration, toxicity, and overall survival benefit. The purpose of this phase II study was to evaluate the activity and safety of cetuximab combined with cisplatin and docetaxel as a first-line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma.

Methods:

Untreated patients with histologically confirmed advanced gastric or gastro-oesophageal adenocarcinoma received cetuximab at an initial dose of 400 mg m⁻² i.v. followed by weekly doses of 250 mg m⁻², cisplatin 75 mg m⁻² i.v. on day 1, docetaxel 75 mg m⁻² i.v. on day 1, every 3 weeks, for a maximum of 6 cycles, and then cetuximab maintenance treatment was allowed in patients with a complete response, partial response, or stable disease.

Results:

Seventy-two patients (stomach 81.9% and gastro-oesophageal junction 18.1%; locally advanced disease 4.2%; and metastatic disease 95.8%) were enrolled. The ORR was 41.2% (95% CI, 29.5–52.9). Median time to progression was 5 months (95% CI, 3.7–5.4). Median survival time was 9 months (95% CI, 7–11). The most frequent grades 3–4 toxicity was neutropenia (44.4%). No toxic death was observed.

Conclusions:

The addition of cetuximab to the cisplatin/docetaxel regimen improved the ORR of the cisplatin/docetaxel doublet in the first-line treatment of advanced gastric and gastro-oesophageal junction adenocarcinoma, but this combination did not improve the TTP and OS. The toxicity of cisplatin/docetaxel chemotherapy was not affected by the addition of cetuximab.     

Randomized trial of weekly docetaxel and cisplatin combined with concurrent 3DCRT in patients with locally advanced esophageal cancer

Objective

This randomized controlled clinical study was to assess and compare the efficacy and safety of two chemoradiotherapy regimens [cisplatin + 5-fluorouracil + 3 dimensional conformal radiation therapy (3DCRT) and cisplatin + weekly docetaxel + 3DCRT] in patients with locally advanced esophageal squamous cell carcinoma.

Methods

A total of seventy-four patients with clinical stages IIB to IIIB esophageal squamous cell carcinoma were enrolled. Chemotherapy for PF group comprised 5-fluorouracil at days 1–5 (250 mg/m²/d) and cisplatin (20 mg/m²) at days 1–3 of every 28-day cycle; full treatment course included 2 cycles. Chemotherapy for DP group comprised docetaxel (20 mg/m²) and cisplatin (20 mg/m²) at days 1, 8, 15, 22, 29, and 36. Both groups treated with concurrent 60 Gy 3DCRT at 200 cGy/d.

Results

Seventy-four patients were enrolled and 71 completed the planned treatment, with a follow-up rate of 95.94%. Short-term curative effect was not statistically significant between the two groups (P = 0.471). The 2-year survival rates were 65.7% and 61.1%, respectively (P = 0.806), 5 years survival rates were 34.29% and 27.78%, respectively (P = 0.221), and there was no significant difference by Fisher test (P = 0.734). As common side effects, incidence rates of radioactive esophagitis and hematological toxicity were lower in DP group.

Conclusion

For locally advanced esophageal cancer patients, current chemoradiotherapy with chemotherapy regimen of weekly docetaxel plus cisplatin has equal curative effect with 5-fluorouracil plus cisplatin, but well-tolerated by reducing side effects such as radioactive esophagitis and bone marrow suppression.     

Preoperative chemotherapy with cisplatin in combination with docetaxel and gemcitabine in locally advanced non-small-cell lung cancer

Despite surgery, both locoregional and distant disease controls remain poor in stage III non-small-cell lung cancer (NSCLC). Preoperative chemotherapy has become an accepted treatment but no established regimen exists. Our objective was to define the activity and feasibility of cisplatin in combination with docetaxel and gemcitabine in stage III NSCLC followed by surgery or radiotherapy. Thirty-two chemotherapy-naive patients with NSCLC (59% stage IIIAN2, 41% stage IIIB) received cisplatin 75 mg/m² on day 1, gemcitabine 1,000 mg/m² on days 1 and 8, and docetaxel 20 mg/m² on days 1, 8 and 15. Patients received induction chemotherapy (3 cycles) before re-evaluation, followed by thoracotomy or thoracic radiotherapy. Radiographic response was 50% and stable disease at computed tomography (CT) scan was observed in 30% of patients. Thirty patients were evaluable for response; thoracotomy was performed in 16 patients (53%) and resection was complete in 8 patients (27%). Grade 3/4 neutropenia, the main hematologic toxicity, occurred in 53% of patients but only 3 patients required hospitalization due to neutropenic fever. Severe non-hematologic toxicity was uncommon. There were 3 treatment-related deaths. To date, 22% of patients remain alive and disease-free with a median follow-up of 13 months. Median survival for all recruited patients was 14 months, with an estimated 1-year survival rate of 60%. The combination of cisplatin/docetaxel/gemcitabine is a welltolerated regimen. Although it has potential serious toxic effects, high response rates and manageable toxicity justify its use in further trials. The Spanish Lung Cancer Group (SLCG) is currently performing a trial with this regimen in stage III disease.     

Weekly paclitaxel for heavily treated advanced or recurrent gastric cancer refractory to fluorouracil, irinotecan, and cisplatin

Background

Although triweekly administration of paclitaxel is approved for gastric cancer in Japan, currently, the drug is often delivered with a weekly schedule because of the equivalent efficacy and lesser toxicity of this dosing schedule as compared with the triweekly administration schedule. Weekly administration of paclitaxel as second-line or first-line chemotherapy for gastric cancer has been reported to yield a response rate of about 20%. Because there has been no report of the efficacy of weekly paclitaxel in the third-line setting, this retrospective study investigated the efficacy and toxicities of weekly paclitaxel used in the third-line setting for the treatment of gastric cancer refractory to all three key drugs, fluorouracil, irinotecan, and cisplatin, used in clinical practice.

Methods

In 85 patients with advanced or recurrent histologically confirmed gastric adenocarcinoma who had failed to respond to prior chemotherapy regimens containing fluorouracil, irinotecan, and cisplatin, paclitaxel (80 mg/m²) was administered weekly, three times, for 3 weeks out of 4.

Results

The median number of courses was 3 (range, 1–38). The overall response rate was 23.2% (19/82) in the patients with measurable lesions, and ascites disappeared in 15 of 48 patients (31.3%). Progression-free survival was 105 days and the median survival time was 201 days from the initiation of paclitaxel administration. Grade 3 or 4 leukopenia, neutropenia, anemia, and thrombocytopenia were observed in 25 (29%), 25 (29%), 37 (44%), and 3 (4%) patients. Other, nonhematological, toxicities were nausea, vomiting, anorexia, sensory neuropathy, fatigue, and febrile neutropenia.

Conclusion

Weekly paclitaxel administration shows activity against advanced gastric cancer also in the third-line setting.     

Salvage treatment with irinotecan/cisplatin versus pemetrexed/cisplatin in patients with non-small cell lung cancer pre-treated with a non-platinum-based regimen in the first-line setting: a randomized phase II study of the Hellenic Oncology Research Group (HORG)

Background

Platinum-based chemotherapy is the standard front-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, non-platinum combinations of third-generation chemotherapeutic agents are considered an alternative therapeutic option for patients who cannot tolerate the toxic effects of platinum compounds. In this study, the efficacy and toxicity of the combination of irinotecan plus cisplatin (IC) was compared to pemetrexed plus cisplatin (PC) regimen, in platinum-naïve patients with advanced NSCLC, who had been previously treated with the combination of a taxane plus gemcitabine.

Patients and methods

A total of 124 patients with locally advanced or metastatic NSCLC were randomly assigned to either irinotecan 110 mg/m² on day 1 and 100 mg/m² on day 8 plus cisplatin 80 mg/m² on day 8 every 3 weeks (IC arm) or pemetrexed 500 mg/m² plus cisplatin 80 mg/m² on day 1 every 3 weeks (PC arm). The primary endpoint of the study was the overall response rate (ORR).

Results

The ORR and median progression-free survival (PFS) in the IC arm were 18 % and 3.3 months, respectively, while in the PC arm were 19 % and 4.2 months (p = ns). Median overall survival (OS) was significantly higher in patients with PC (6.9 vs. 10.9; p = 0.013). PC regimen had a better toxicity profile compared to IC, with a statistically significant lower incidence of grade 3/4 neutropenia (3 vs. 31 %; p = 0.0001) and diarrhea (1.6 vs. 14.7 %, p = 0.018).

Conclusions

In patients with advanced NSCLC pretreated with docetaxel/gemcitabine, the combination of pemetrexed/cisplatin is associated with increased OS and is better tolerated than the combination of irinotecan/cisplatin and should be considered as a valid therapeutic option for platinum-naive, previously treated patients.

ClinicalTrials.gov Identifier

NCT00614965.

     

Concurrent cetuximab and radiotherapy after docetaxel-cisplatin induction chemotherapy in stage III NSCLC: Satellite—A phase II study from the Swedish Lung Cancer Study Group

Background

Several attempts to increase the locoregional control in locally advanced lung cancer including concurrent chemotherapy, accelerated fractionation and dose escalation have been made during the last years. As the EGFR directed antibody cetuximab has shown activity concurrent with radiotherapy in squamous cell carcinoma of the head and neck, as well as in stage IV NSCLC combined with chemotherapy, we wanted to investigate radiotherapy with concurrent cetuximab in locally advanced NSCLC, a tumour type often over expressing the EGF-receptor.

Methods

Between February 2006 and August 2007 75 patients in stage III NSCLC with good performance status (PS 0 or 1) and adequate lung function (FEV1 > 1.0) were enrolled in this phase II study at eight institutions. Treatment consisted of 2 cycles of induction chemotherapy, docetaxel 75 mg/m² and cisplatin 75 mg/m² with 3 weeks interval. An initial dose of cetuximab 400 mg/m² was given before start of 3D-CRT to 68 Gy with 2 Gy per fraction in 7 weeks concurrent with weekly cetuximab 250 mg/m². Toxicity was scored weekly during radiotherapy (CTC 3.0), and after treatment the patients were followed every third month with CT-scans, toxicity scoring and QLQ.

Results

Seventy-one patients were eligible for analysis as four were incorrectly enrolled. Histology: adenocarcinoma 49%, squamous cell carcinoma 39% and other NSCLC 12%. The majority had PS 0 (62.5%), median age 62.2 (42-81), 50% were women and 37% had a pre-treatment weight loss > 5%. Toxicity: esophagitis grade 1-2: 72%; grade 3: 1.4%. Hypersensitivity reactions grade 3-4: 5.6%. Febrile neutropenia grade 3-4: 15.4%. Skin reactions grade 1-2: 74%; grade 3: 4.2%. Diarrhoea grade 1-2: 38%; grade 3: 11.3%. Pneumonitis grade 1-2: 26.8%; grade 3: 4.2%; grade 5: 1.4%. The median follow-up was 39 months for patients alive and the median survival was 17 months with a 1-, 2- and 3-year OS of 66%, 37% and 29% respectively. Until now local or regional failure has occurred in 20 patients and 22 patients have developed distant metastases. Weight loss, PS and stage were predictive for survival in univariate as well as in multivariate analysis.

Conclusion

Induction chemotherapy followed by concurrent cetuximab and RT to 68 Gy is clearly feasible with promising survival. Toxicity, e.g. pneumonitis and esophagitis is low compared to most schedules with concurrent chemotherapy. This treatment strategy should be evaluated in a randomised manner vs. concurrent chemoradiotherapy to find out if it is a valid treatment option.