Resultados a largo plazo de radioterapia y quimioterapia concomitante en cáncer microcítico de pulmón, enfermedad limitada al tórax, fuera de ensayos clínicos

Introduction

Chemotherapy combined with radiotherapy can improve local control and survival in patients with small cell lung cancer (SCLC).

Material and methods

We used cisplatin and etoposide (PE) with concurrent thoracic radiation therapy (TRT) followed by prophylactic cranial irradiation (PCI) in patients achieving a complete response. The objective was to evaluate the efficacy and toxicity of this regime in patients with localised SCLC. Patients (n=89) diagnosed with localised SCLC were treated with PE (4 to 6 cycles) together with TRT (50–60 Gy).

Results

The response rate was 92% (62%CR, 30%PR). The 20 patients with CR had PCI administered. Grade III–IV toxicities were 68% neutropenia, 23% thrombocytopenia, 23% anaemia and 24% severe dysphagia. Median overall survival rate was 17 months (probable survival rate of 35% at 2 years).

Conclusions

The treatment is feasible and provides acceptable survival rates despite the accompanying toxicity. It is recommended that PCI be provided for all patients achieving complete response.     

Soft tissue sarcomas and therapeutic management: is there a place for systemic chemotherapy in an adjuvant setting?

Introduction

Extremity soft tissue sarcomas (STS) represent a rare, heterogeneous malignancy. Surgery is the primary treatment for patients with no evidence of metastatic disease but 50% of patients with high-risk tumors will relapse and develop metastatic disease. Adjuvant chemotherapy aims to lessen the recurrence of cancer after surgery with or without radiotherapy. The objective of this review was to assess the effect of adjuvant chemotherapy in adults with resectable soft tissue sarcoma after such local treatment.

Materials and methods

Pub Med searches were done to identify all randomized controlled phase III trials (RCTs) published, and presented in various international conferences, comparing surgery plus adjuvant systemic chemotherapy to surgery alone (S) for resectable soft tissue sarcoma. The following keywords: adjuvant therapy, chemotherapy, soft tissue sarcoma were used to access the principal phase III study and meta-analysis based on individual and published data.

Results

Three randomized phase III trials and three meta-analyses were identified, comparing adjuvant chemotherapy to observation after curative resection. The majority of studies indicate some benefit with chemotherapy, particularly in the relapse-free survival rate, but no survival benefit was observed in the chemotherapy group relative to the control group. Quality of initial surgery is the most important prognostic and predictive factor for Relapse Free Survival (RFS) and Overall Survival (OS).

Conclusion

Compared to surgery alone, the role and value of adjuvant chemotherapy have not yet been established and cannot be recommended outside the context of a clinical trial.     

Do patients whose tumor achieved a pathological response relapse at specific sites? A substudy of the EORTC 10994/BIG-1-00 trial

Purpose

To determine the sites of first distant relapse in patients with or without pCR following neoadjuvant chemotherapy in breast cancer patients enrolled in the EORTC 10994/BIG-1-00 trial.

Methods

We included patients enrolled in the EORTC 10994/BIG-1-00 trial who received at least one chemotherapy cycle before surgery and who had been diagnosed with a distant relapse. pCR was defined as no evidence of residual invasive cancer in the primary tumor and axillary lymph nodes with or without residual ductal carcinoma in situ. Site of first distant relapse was categorized as ‘soft tissue,’ ‘visceral,’ ‘skeletal,’ ‘central nervous system (CNS),’ and ‘other.’ The association between relapse site and achievement of pCR was assessed using multivariate logistic regression models for molecular subtypes classification and preceding locoregional recurrence.

Results

The study included 383 (21%) eligible patients out of the 1856 randomized, of whom 28 (7%) had achieved pCR. Median follow-up was 5.4 years. Achievement of pCR was associated with a trend towards a decreased presentation of skeletal metastases [21% (pCR) vs. 50% (non-pCR), OR 0.32, adjusted p value = 0.071] and an increase in the proportion of patients with CNS metastases as first distant relapse site (21% vs. 9%, OR 2.39, adjusted p value = 0.183). Patients with pCR were more likely to present with only one relapse location category when compared to non-pCR (86% vs. 69%).

Conclusion

Patients that achieved a pCR appeared less likely to present with skeletal metastases and more frequently presented with CNS metastases as first site of distant relapse, even after adjustment for molecular subtypes.

     

Etoposide plus cisplatin with concurrent radiotherapy in the treatment of small-cell lung cancer

Introduction

Since the decade of the 80's, the etoposide plus cisplatinum regimen has been the standard treatment in patients with localised small-cell lung cancer (SCLC). Randomised trials have demonstrated the benefit of chemotherapy in combination with hyper-fractionated radiotherapy in this subset of patients.

Material and methods

Between January 1993 and June 1999, a total of 59 patients with localised SCLC were recruited into the study. All patients received 4 cycles of chemotherapy every 21 days. The first cycle was administered concurrently with hyper-fractionated radiotherapy. Prophylactic cranial irradiation (PCI) was administered subsequently when complete response was obtained.

Results

The proposed treatment schedule was successfully accomplished in 54 patients. The more important toxicities noted were oesophagitis and myelotoxicity, febrile neutropenia in 6 patients (10%), and oesophagitis grade IV in 9 patients (15%). Complete response was achieved in 39 cases (72%) and partial response in 11 (20%). Median survival was 20 months.

Conclusions

We conclude that the schedule combining etoposide + cisplatin with concurrent hyperfractionated radiotherapy is the best therapeutic scheme currently on offer in the management of patients with localised SCLC.     

Prognostic factors for patients in postoperative brain metastases from surgically resected non-small cell lung cancer

Background

Postoperative recurrence in non-small cell lung cancer (NSCLC) reduces the life expectancy of patients. In this retrospective study, we investigated the prognostic factors in patients with postoperative brain metastases from surgical resected non-small cell lung cancer (NSCLC).

Methods

We conducted a retrospective chart review of patients who had undergone resection for NSCLC between April 2004 and February 2009 and found 65 had experienced postoperative brain metastases by March 2010. We reviewed these patients for clinicopathological information, treatments and responses to treatment, and overall survival.

Results

The 5-year survival rate after the diagnosis of brain metastases was 15.4 %. Significantly favorable prognostic factors for patients after a diagnosis of brain metastases included female gender, adenocarcinoma, a small number (1–3) of brain metastases, no extracranial metastasis at the diagnosis of brain metastases, radiation treatment (whole-brain radiation and/or stereotactic irradiation), and local treatment [stereotactic irradiation and/or surgical operation (craniotomy)]. Furthermore, in patients with only brain metastases as the postoperative initial recurrence, the favorable positive prognostic factors included a small number (1–3) of brain metastases, adjuvant chemotherapy, chemotherapy (including adjuvant and other chemotherapy and excluding epidermal growth factor receptor–tyrosine kinase inhibitors), and local treatment.

Conclusions

Our study found that the foregoing clinical characteristics in postoperative brain metastases and the administration of treatment contributed to patient life expectancy.     

Kleinzelliges Lungenkarzinom

Background

Prognostic improvements for patients with small cell lung cancer (SCLC) have been achieved within the last decade especially due to the use of radiotherapeutic treatment options.

Methods

In this article, an overview of the approved and current therapeutic approaches for the treatment of SCLC is presented.

Results

Given the high potential for proliferation and metastatic spread in SCLC, systemic chemotherapy, preferably with a platinum/etoposide combination, is still the therapeutic basis. In limited stage disease this is performed, if possible, simultaneously with thoracic radiotherapy (TRT) followed by prophylactic cranial irradiation (PCI). In extended stage disease (ED), TRT also has therapeutic value for those patients who respond to chemotherapy. PCI generally shows a reduction in the risk for cerebral metastases, but is with regard to the improvement of overall survival in ED controversial.

Conclusion

Chemotherapy together with radiooncology is of substantial relevance for survival of SCLC patients.

     

Feasibility of mFOLFOX6 as the adjuvant treatment after curative resection of metastases from colorectal cancer in Japanese patients

Background

An oxaliplatin-based regimen as the adjuvant treatment for stage III colon cancer demonstrated a survival advantage over fluorouracil (FU) and leucovorin (LV) in the MOSAIC and NSABP C-07 trials. For adjuvant treatment after the resection of metastases from colorectal cancer), active chemotherapy regimens such as FOLFOX are recommended. However, the safety data of FOLFOX are insufficient for its use after metastasectomy of colorectal cancer in Japanese patients. The aim of this study was to evaluate the safety of mFOLFOX6 for adjuvant treatment after the resection of metastases from colorectal cancer.

Methods

Among 67 consecutive patients who received mFOLFOX6 as the adjuvant treatment after resection of metastases from colorectal cancer between September 2002 and March 2009 in our institution, 51 patients who had not received preoperative chemotherapy were reviewed. The mFOLFOX6 treatment comprised oxaliplatin 85 mg/m² and l-leucovorin 200 mg/m² given intravenously over a 2-h period on day 1, followed by a 5-FU bolus of 400 mg/m² and a 46-h infusion of 5-FU 2400 mg/m², every 2 weeks for up to 12 cycles.

Results

National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTC) grade 3–4 toxicities per patient were: peripheral neuropathy 8%, allergic reaction 4%, aspartate transaminase (AST) 4%, febrile neutropenia 4%, nausea 2%, anorexia 2%, fatigue 2%, alanine transaminase (ALT) 2%, bilirubin 2%, neutrophils 49%, leukocytes 6%, and hemoglobin 2%; 71% of the patients completed the scheduled 12 cycles.

Conclusion

Adjuvant therapy with mFOLFOX6 after resection of metastases from colorectal cancer is feasible for Japanese patients.     

Non-surgical approach to small cell carcinoma of the esophagus: does this rare disease have the same tumor behavior as SCLC?

Background

We conducted a retrospective analysis to clarify the clinical profile of a nonsurgical approach to small cell carcinoma of the esophagus (SCEC).

Patients and methods

SCEC patients in our database were reviewed. Consistent with the standard approach to small cell carcinoma of the lung (SCLC), chemoradiotherapy was the first choice for limited disease (LD)-SCEC in our institution while chemotherapy was the first choice for extensive disease (ED)-SCEC. Our strategy did not include prophylactic cranial irradiation.

Results

Eighteen patients were treated between January 1996 and December 2006, of whom 10 had LD-SCEC and 8 had ED-SCEC. Regarding response to chemoradiotherapy in patients with LD-SCEC, CR rate at the primary site was 90% (9/10) and total CR rate was 80% (8/10). With a median follow-up period of 55.3 months, median survival time in LD-SCEC and ED-SCEC patients was 17.3 and 13.9 months, respectively, showing no significant difference (p = 0.57). Brain metastases occurred in only one patient. On follow-up, eight patients with LD-SCEC and seven with ED-SCEC died of disease. Only 2 patients died of local progression, while the remaining 13 died of disease progression of distant metastases.

Conclusion

Despite providing good local control, chemoradiotherapy appeared to have insufficient potential to cure LD-SCEC. Prophylactic brain irradiation for SCEC is unnecessary.     

Usage of Prophylactic Cranial Irradiation in Elderly Patients With Small-cell Lung Cancer

Background

Prophylactic cranial irradiation (PCI) reduces the risk of overt brain metastases in patients with small-cell lung cancer (SCLC) and is currently recommended in guidelines for both limited and extensive disease. Given the concerns about the greater frequency of neurologic side effects in elderly patients, we studied the association among age, PCI usage, and survival for SCLC patients in the Netherlands.

Neoadjuvant chemotherapy and preoperative chemoradiotherapy in resectable carcinoma of the rectum

Introduction

The effectiveness of neoadjuvant chemotherapy (Mayo clinic schedule) and continuous oral chemotherapy (tegafur 400 mg and folinic acid 15 mg every 12 hours) administered during preoperative radiotherapy (4,500 cGy over 5 weeks) were studied

Materials and methods

A total of 53 patients with surgically-resectable rectal adenocarcinoma were treated.

Results

Toxicities of ≤ grade II were lower with neoadjuvant chemotherapy while the chemoradiotherapy had higher toxicity rates including grade III diarrhoea (4%), grade III mucositis (4%), and grade III–IV neutropenia (9%). Symptom improvement ocurred in 38% of patients after neoadjuvant chemotherapy coparative with 55% following the first week of chemoradiotherapy. Surgery was curative in 97% of the patients: abdominoperineal amputation in 24 patients (47%) and conservative surgery in 28 (53%). Down-staging ocurred in 24 patients (46%), and 7 patients (14%) showed pathological complete response. Overvall survival at 5 years, with a median follow-up of 50 months, was 70% (cancer-specific survival was 75%) with significant differences recorded between N+ and N0 patients (56% and 76%, respectively; p<0.001), and between T-0-1-2 and T3 patients (73% and 56%, respectively; p<0.001). Only 2 patients (3%) had local relapse.

Conclusion

This treatment scheme was well tolerated and had high rate of local control and longterm times.     

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.     

Management of Anorectal Melanoma: Report of 17 Cases and Literature Review

Background

Primary anorectal melanoma is a rare and aggressive disease. It accounts for 0.5% of all rectal tumors. They are very agressive tumors with poor prognosis. The aim of this study is to report the clinical and evolutionary profile and therapeutical approach of these tumors.

Patients and Methods

A retrospective study of 17 patients with anorectal melanoma diagnosed between January 1998 and December 2007 was performed. The signs and symptoms, diagnostic study, and surgical and medical treatments were analyzed.

Results

The average age was 58?years. Sex ratio was 12 men per five women. Patients had symptoms present for an average of 6?months. The most common symptom was rectal bleeding. According to Slingluff classification, five patients had stage I (localized tumor), four cases had stage II (regional nodes metastasis), and eight cases had stage III (distant metastasis). Seven patients have radical surgery. Only two patients received adjuvant immunotherapy. Eight patients received palliative chemotherapy based on dacarbazine or cisplatinum. The median survival was 8?months.

Conclusion

Prognosis of anorectal melanoma is still very poor. However, some patients when treated by radical resection may experience long-term survival. The use of adjuvant immunotherapy needs large collaborative studies in view of the rarity of the tumor.     

A feasibility study of postoperative chemotherapy with S-1 and cisplatin (CDDP) for gastric carcinoma (CCOG0703)

Background

The outcome of stage III gastric cancer patients treated by D2 dissection followed by adjuvant chemotherapy with S-1 remains unsatisfactory. Moreover, some patients with a preoperative diagnosis of stage II/III turn out to be stage IV after surgical exploration, and a standard postoperative treatment for this population has not been established.

Methods

A feasibility study of postoperative S-1/cisplatin (CDDP) was performed with patients who underwent gastrectomy for what turned out to be a stage IV gastric cancer. The primary endpoint of the trial was the relative dose intensity during five courses of S-1/CDDP. Several criteria to skip, postpone, or reduce the dose had been predetermined.

Results

Between 2007 and 2009, 31 patients were accrued, including 19 patients who were positive for peritoneal washing cytology, 6 with peritoneal seeding, 5 with metastasis to the paraaortic nodes, and 4 with other distant metastases. Only 7 patients completed five cycles as planned (median, two cycles). The median relative dose intensities of S-1 and CDDP were 37% and 40%, respectively. Causes of treatment failure were failure to fulfill criteria for starting a new course within 5 weeks of the last administration of S-1 in 7, patient refusal in 6, disease recurrence/progression in 4, need to reduce dose by two levels in 4, and two successive skips of CDDP in 3 patients. The median progression-free survival time of all patients was 363 days.

Conclusions

Although promising in the neoadjuvant and advanced/metastatic setting, S-1/CDDP is too toxic as a postgastrectomy treatment for Japanese patients.     

Induction chemotherapy with carboplatin and taxol followed by radiotherapy and concurrent weekly carboplatin?+?taxol in locally advanced nasopharyngeal carcinoma

Purpose

Aim of this study was the clinical evaluation of carboplatin?Ctaxol combination in a neoadjuvant and concomitant setting with conventional radiotherapy in loco-regionally advanced nasopharyngeal carcinoma (A-NPC).

Methods

Thirty patients were treated with three cycles of carboplatin (AUC6) plus taxol (175?mg/m²) on day 1 every 3?weeks, followed by weekly carboplatin (AUC1) plus Taxol (60?mg/m2) and concomitant radiotherapy (70?Gy).

Results

We observed the objective complete response rates of 33% (after chemotherapy) and 87% (after chemo-radiotherapy). Treatment tolerability and toxicity were controllable. Three- and five-year progression-free survival were 80 and 75%, respectively, and 3- and 5-year overall survival were 85 and 80% (follow-up 49.5?months). Five-year loco-regional control was 90.3%, and five-year distant metastases?Cfree survival was 85%.

Conclusions

Neoadjuvant chemotherapy with such protocol represents a feasible, efficient treatment for patients with A-NPC, ensuring excellent loco-regional disease control and overall survival with low incidence of distant metastases.     

Centromere protein-A, an essential centromere protein, is a prognostic marker for relapse in estrogen receptor-positive breast cancer

Introduction

Centromere protein A (CENP-A), an essential centromere protein, has been associated with high grade cancers. This study was undertaken to determine if CENP-A is a prognostic factor for breast cancer patients not receiving systemic therapy or predictive of response to tamoxifen or neoadjuvant chemotherapy.

Methods

mRNA levels of CENP-A and CENP-B, a centromere protein that binds independently of CENP-A, were measured in breast cancer specimens from 484 patients receiving no systemic therapy, 276 patients receiving tamoxifen, and 233 patients treated with neoadjuvant chemotherapy. Associations between CENP-A, CENP-B, Ki-67, relapse, and chemotherapy response were determined.

Results

CENP-A but not CENP-B was higher in estrogen receptor (ER)-negative tumors than ER-positive tumors and positively correlated with Ki-67 expression. Among patients with ER-positive disease who received no systemic therapy or tamoxifen, higher levels of CENP-A were associated with lower rates of 5-year distant relapse free survival (DRFS). On multivariate analyses including Ki-67, high CENP-A expression had a hazard ratio of 10.9 for relapse in patients with ER-positive disease not receiving systemic therapy (95% CI, 2.86 to 41.78; P = 0.00047) and 1.64 for patients with ER-positive disease receiving tamoxifen (95% CI, 0.99 to 2.71; P = 0.054). CENP-A was not an independent prognostic marker in ER-negative tumors. For both ER-positive and ER-negative tumors, CENP-A was not a significant independent predictor of chemotherapy response.

Conclusions

CENP-A was a significant independent prognostic marker for patients with ER-positive breast cancer not treated with systemic therapy but had limited predictive value in tamoxifen treated patients and was not predictive of response to neoadjuvant chemotherapy.     

Long-term results with oral fluoropyrimidines and oxaliplatin-based preoperative chemoradiotherapy in patients with resectable rectal cancer. A single-institution experience

Introduction

Neoadjuvant 5-FU-based chemoradiotherapy in resectable rectal cancer (RC) is a standard of treatment. The use of oral fluoropyrimidines and new agents such as oxaliplatin may improve efficacy and tolerance.

Material and methods

Between 1999 and 2009, 126 RC patients with T3?CT4 and/or N+ disease were given three successive protocols: UFT (32), UFT-oxaliplatin (75) and capecitabine-oxaliplatin (19), alongside 45 Gy of radiotherapy; with surgery 4?C6 weeks after. Adjuvant treatment was given in all patients. The primary objective was pathologic complete response (pCR).

Results

Preoperative therapy was well tolerated, with no toxic deaths and a 15% grade 3?C4 toxicity rate. Eighty-five percent of patients received the full chemotherapy dose, 56% had an abdominoperineal resection, 6% reinterventions and 57% received the full adjuvant chemotherapy planned. The pCR rate was 13%. The downstaging rate was 80%; 8% had progression of disease. The relapse rate was 20%, with local relapse in 6%. By 5 years of followup, 92% of relapses had occurred. Median follow-up was 73 months, 5- and 10-year disease-free survival rates were 75% and 50%, and 5- and 10-year overall survival rates were 79% and 66% respectively. There was no benefit from the use of oxaliplatin regarding survival or pCR rates. Older patients had worse long-term outcomes.

Conclusions

Neoadjuvant chemoradiotherapy with oral fluoropyrimidines and oxaliplatin is feasible and well tolerated. The risk of early progression is low. However, there was no added benefit with the use of oxaliplatin. There were no relapses in patients with pCR. The role of adjuvant chemotherapy is unclear.     

A phase II study of docetaxel and oxaliplatin combination in recurrent gastric cancer patients after fluoropyrimidine and/or cisplatin adjuvant treatment: a Korean Cancer Study Group Protocol ST06-02

Background

Surgery alone is no longer an adequate standard of care for patients with resectable gastric cancer. Thus, research efforts should focus on which regimens are the most effective for patients with recurrent gastric cancer after combined treatment with surgery and perioperative or adjuvant chemotherapy.

Methods

Patients with histologically confirmed and measurable advanced gastric cancer who showed a relapse even after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy received docetaxel (35?mg/m²) intravenously on day 1 and 8 plus oxaliplatin (100?mg/m²) intravenously on day 1 every 3?weeks until disease progression or unacceptable toxicity.

Results

A total of 34 patients with relapsed advanced gastric cancer who had received adjuvant chemotherapy with fluoropyrimidine and/or cisplatin for a median of 6?months (range, 1–48?months) were enrolled in this trial; 22 (64.7?%) patients had been exposed to both agents. Their median age was 58?years (range, 50–68?years). The overall response rate was 55.9?% (95?% confidence interval (CI), 38.3–73.5?%), including 1 complete response and 18 partial responses. At a median follow-up duration of 28.5?months (range, 9.2–50.7?months), the median progression-free survival for all patients was 5.3?months (95?% CI, 4.4–6.1?months) and the median overall survival was 13.8?months (95?% CI, 11.1–16.4?months). The most common grade 3 or 4 hematologic and nonhematologic toxicities were neutropenia (47.1?%) and diarrhea (17.6?%), respectively. Five patients (14.7?%) experienced febrile neutropenia.

Conclusions

Docetaxel and oxaliplatin combination chemotherapy was active and tolerable in patients with recurrent gastric cancer after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy.     

High incidence of regional and in-transit lymph node metastasis in patients with alveolar rhabdomyosarcoma

Background

Rhabdomyosarcoma has different extension patterns, including a higher propensity for lymph nodes metastasis, compared with other types of soft tissue sarcoma. The aims of this study were to investigate the patterns of regional and distant metastasis in patients with rhabdomyosarcomas, particularly lymphatic route metastasis, and clarify the clinical factors that affect the pattern of metastasis.

Methods

Forty-four patients with rhabdomyosarcomas were enrolled in this study. The mean age of the patients was 26 (range 1–69) years, and 18 were males. The histological subtypes included alveolar (17 patients), embryonal (10 patients), pleomorphic (7 patients), and unknown (10 patients). Based on location, the sarcomas were divided into three groups: extremity (17 cases), favorable prognosis (10 cases), and unfavorable prognosis (15 cases). There were three cases (7 %) of local relapse, ten cases of regional lymph node relapse, and three cases of in-transit metastasis (total 30 %). Twenty-one patients (48 %) developed distant metastases. Initial sites of metastases were bone (9 patients, 20 %), lung (5 patients), and bone marrow dissemination (5 patients). Clinico-pathological variables affecting relapse patterns were analyzed.

Results

Of the three cases of local relapse, two were alveolar type and one was unknown. The three cases of in-transit metastasis were all alveolar type. Patients with alveolar type had a significantly high propensity for lymph node metastasis (P = 0.027). Excluding the pleomorphic type, alveolar type was still a significant factor for lymph node metastasis (P = 0.017).

Conclusion

Physicians should be aware of in-transit spread, particularly in patients with alveolar-type rhabdomyosarcoma. Novel treatment modalities are required to detect and treat in-transit metastasis.     

Paclitaxel combined with ifosfamide in anthracycline- and docetaxel-pretreated metastatic breast cancer: activity independence of prior docetaxel resistance

Background

We evaluated the efficacy and tolerability of combined paclitaxel and ifosfamide in anthracycline- and docetaxel-pretreated metastatic breast cancer (MBC).

Methods

Patients received paclitaxel (175 mg/m² i.v. in a 3-h infusion) on day 1 and ifosfamide (1.5 g/m² i.v. in a 15-min infusion) on days 1–3, every 3 weeks for a maximum of nine cycles. The tumor response was assessed every two cycles.

Results

We enrolled 34 patients with a median age of 50 years. Thirty patients had visceral metastases. Anthracycline- and docetaxel-based chemotherapy had previously been administered to 18/13 and 13/21 patients, respectively, in (neo)adjuvant/metastatic settings. Three patients had not previously received anthracycline due to abnormal cardiac functions. A total of 174 cycles of chemotherapy were delivered with a median of six cycles. The response rate under the intent-to-treat analysis was 23.5% (all partial responses) with a median response duration of 14 months. The disease control rate was 70.6%. The median progression-free and overall survival were 5.9 and 8.5 months, respectively. There was no apparent relationship between activity and prior docetaxel resistance. The incidence of grade III/IV neutropenia was 46.6% (81 of 174 cycles) with febrile neutropenia of only 1.7%. Major grade III/IV non-hematological toxicities included peripheral neuropathy (6 of 34 patients) and infection (4 of 34 patients). There were no treatment-related deaths.

Conclusion

Paclitaxel combined with ifosfamide was effective and tolerable in anthracycline-/docetaxel-pretreated MBC. Overcoming docetaxel resistance by using paclitaxel in combination with ifosfamide needs to be addressed through further investigation.     

Phase II study of adjuvant vinorelbine and cisplatin in Japanese patients with completely resected stage II and III non-small cell lung cancer

Purpose

Adjuvant vinorelbine and cisplatin chemotherapy is recognized as a standard regimen for patients with completely resected stage II and III non-small cell lung cancer (NSCLC). However, efficacy of adjuvant chemotherapy in Japanese phase III trials with cisplatin-containing regimen has been controversial, and data are limited on the long-term outcome of adjuvant vinorelbine and cisplatin chemotherapy for NSCLC patients.

Methods

This was a single-arm phase II study in patients with completely resected pathological stage II or III NSCLC, who had not received prior chemotherapy or radiotherapy. Patients received 4 cycles of vinorelbine [25 mg/m² of body surface area (BSA)] and cisplatin (40 mg/m² of BSA) on days 1 and 8, every 4 weeks. Primary end point was the 3-year relapse-free survival; secondary end points were overall survival and safety.

Results

Between December 2006 and January 2011, 60 patients (40 men and 20 women, median age 64 years) were enrolled; all patients were evaluable for survival and safety. Three-year relapse-free survival rate was 55.0 % (95 % confidence interval 42.4–67.6 %). Three- and five-year overall survival rates were 83.3 and 77.8 %, respectively. There were no chemotherapy-related deaths, and adverse effects were acceptable.

Conclusions

Adjuvant vinorelbine and cisplatin chemotherapy was safe and showed a valid relapse-free survival rate. This regimen could be used as a standard regimen and deserves to be a control arm of trials on adjuvant chemotherapy in the Japanese NSCLC patient population.