Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy

BACKGROUND:

Peritoneal carcinomatosis (PC) from nonovarian malignancies long has been regarded as a terminal disease. Over the past decade, new locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved that have demonstrated improved survival.

METHODS:

A retrospective, multicenter cohort study was performed in French‐speaking institutions to evaluate toxicity and principal prognostic factors after cytoreductive surgery and PIC (hyperthermic intraperitoneal chemotherapy [HIPEC] and/or early postoperative intraperitoneal chemotherapy [EPIC]) for PC from nongynecologic malignancies.

RESULTS:

The study included 1290 patients from 25 institutions who underwent 1344 procedures between February 1989 and December 2007. HIPEC was performed in 1154 procedures. The principal origins of PC were colorectal adenocarcinoma (N = 523), pseudomyxoma peritonei (N = 301), gastric adenocarcinoma (N = 159), peritoneal mesothelioma (N = 88), and appendiceal adenocarcinoma (N = 50). The overall morbidity and mortality rates were 33.6% and 4.1%, respectively. In multivariate analysis, patient age, the extent of PC, and institutional experience had a significant influence on toxicity. The overall median survival was 34 months; and the median survival was 30 months for patients with colorectal PC, not reached for patients with pseudomyxoma peritonei, 9 months for patients with gastric PC, 41 months for patients with peritoneal mesothelioma, and 77 months for patients with PC from appendiceal adenocarcinoma. Independent prognostic indicators in multivariate analysis were institution, origin of PC, completeness of cytoreductive surgery, extent of carcinomatosis, and lymph node involvement.

CONCLUSIONS:

A therapeutic approach that combined cytoreductive surgery with PIC was able to achieve long‐term survival in a selected group of patients who had PC of nonovarian origin and had acceptable morbidity and mortality. The current results indicated that this treatment should be centralized to institutions with expertise in the management of PC. Cancer 2010. © 2010 American Cancer Society.     

Xeroderma pigmentosum complementation group C single-nucleotide polymorphisms in the nucleotide excision repair pathway correlate with prolonged progression-free survival in advanced ovarian cancer

BACKGROUND:

The nucleotide excision repair (NER) pathway is the principal DNA repair pathway for removing bulky platinum DNA adducts. Suboptimal DNA repair may lead to improved response to platinum agents. The objective of this study was to determine whether single‐nucleotide polymorphisms (SNPs) in NER pathway genes could be markers of platinum response in ovarian cancer.

METHODS:

The authors identified patients with advanced‐stage, papillary serous ovarian cancer who underwent primary cytoreductive surgery followed by platinum‐based chemotherapy. DNA was isolated from peripheral blood specimens. Twenty‐two SNPs within NER genes (xeroderma pigmentosum [XP] complementation group A [XPA], XPB/excision repair cross‐complementing rodent repair deficiency, complementation group 3 [ERCC3], XPC, XPD/ERCC2, XPF/ERCC4, XPG/ERCC5, Cockayne syndrome group B protein [CSB]/ERCC8, ERCC1) were genotyped using polymerase chain reaction analysis.

RESULTS:

In total, 139 patients with stage III and IV papillary serous ovarian cancer were genotyped. The XPC (reference SNP 3731108 [rs3731108]) adenosine‐guanine (AG)/AA genotype versus the GG genotype was associated with prolonged a progression‐free survival (PFS) of 21.3 months versus 13.4 months (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.42‐0.95; P = .03). The XPC (rs1124303) guanosine‐thymidine (GT)/GG genotype versus the TT genotype was associated with a prolonged PFS of 22.8 months versus 14.9 months (HR, 0.47; 95% CI, 0.24‐0.94; P = .03). The XPC poly(AT) (PAT) (?/+)/(?/?) genotype versus the (+/+) genotype was associated with a prolonged PFS of 17 months versus 11.6 months (HR, 0.56; 95% CI, 0.36‐0.89; P = .01). The XPF/ERCC4 (rs12926685) cytidine‐thymidine (CT)/CC genotype versus the TT genotype was associated with a prolonged PFS of 16.7 months versus 12.4 months (HR, 0.63; 95% CI, 0.41‐0.95; P = .03). On multivariate analysis adjusting for breast cancer (BRCA) gene and cytoreductive surgery status, the XPC SNPs remained significantly associated with prolonged PFS.

CONCLUSIONS:

The current results indicated that XPC is a key component of the NER pathway that participates in DNA damage repair. SNPs in the XPC gene may represent novel markers of ovarian cancer response to platinum‐based chemotherapy. Cancer 2012;. © 2011 American Cancer Society.     

Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis

BACKGROUND:

Survival benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion was demonstrated by a prospective randomized trial for colorectal peritoneal carcinomatosis. Because of a recent substantial improvement in chemotherapy, the authors analyzed treatment options of colorectal carcinomatosis in the current era.

METHODS:

Consecutive patients with colorectal carcinomatosis treated by cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion from 2001 to 2007 were included. The control group patients with carcinomatosis received contemporary chemotherapy alone. Overall survival was the primary endpoint.

RESULTS:

All patients underwent systemic chemotherapy. The cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion group (n = 67) was similar to the control group (n = 38) in sex, tumor grade, site of tumor origin, T status, and N status. The control group was, however, older (59 vs 51 years; P<.001). Median survival measured from the diagnosis of peritoneal disease was longer with cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion (34.7 months vs 16.8 months; P<.001). Presence of liver metastasis was a significant negative predictor of survival (hazard ratio, 2.13).

CONCLUSIONS:

The authors concluded that 1) contemporary chemotherapy is associated with prolonged survival among patients with carcinomatosis as compared with historical controls, and 2) addition of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion to modern chemotherapy regimens may significantly prolong survival. Cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion and systemic chemotherapy are not competitive therapies, and they both have a role in a multidisciplinary approach to patients with carcinomatosis. Cancer 2010. © 2010 American Cancer Society.     

Second-line chemotherapy with fluorouracil, leucovorin, and irinotecan (FOLFIRI regimen) in patients with advanced small bowel adenocarcinoma after failure of first-line platinum-based chemotherapy: a multicenter AGEO study

BACKGROUND:

Small bowel adenocarcinoma (SBA) is a rare tumor with poor prognosis. First‐line platinum‐based chemotherapy is active in patients with advanced SBA, but data regarding second‐line chemotherapy are lacking. The aim of this study was to evaluate the efficacy and tolerability of fluorouracil, leucovorin, and irinotecan (FOLFIRI regimen) as second‐line chemotherapy in patients with advanced SBA.

METHODS:

We analyzed all consecutive patients who received second‐line chemotherapy with FOLFIRI among 93 patients with advanced SBA included from 1996 to 2008 in a previous retrospective multicenter study. Progression‐free survival (PFS) and overall survival (OS) were estimated from the start of second‐line chemotherapy using the Kaplan‐Meier method. Cox models were applied for multivariate analyses.

RESULTS:

Among 51 patients who received second‐line chemotherapy, 28 patients (male, 57%; median age, 54 years; metastatic disease, 96%) were treated with FOLFIRI after progression (n = 24) or limiting toxicity (n = 4) to first‐line FOLFOX (n = 19) or LV5FU2‐cisplatin (n = 9). Grade 3‐4 toxicity was observed in 48% of patients (grade 3‐4 neutropenia, 37%). After a median follow‐up of 21.5 months, all patients had tumor progression, and 22 patients died. Objective response rate was 20%, and disease control rate was 52%. Median PFS and OS were 3.2 and 10.5 months, respectively. No clinical, biological, or tumor characteristics were associated with PFS or OS by multivariate analysis.

CONCLUSIONS:

Second‐line chemotherapy with FOLFIRI produced disease control in half of patients with advanced SBA after failure with first‐line platinum‐based chemotherapy. Nevertheless, the short median PFS warrants the evaluation of other treatments including targeted therapies. Cancer 2011. © 2010 American Cancer Society.     

Phase II Trial of Adjuvant Oral Thalidomide Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Disease from Colorectal/Appendiceal Cancer

Purpose

This phase II single-institution trial of adjuvant thalidomide after cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with appendiceal and colorectal malignancies sought to detect an improvement in progression-free survival (PFS) from 7 to 12 months.

Methods

Eligible patients received CS, HIPEC, and baseline imaging, followed by pretreatment thalidomide counseling. All participants were then started on a 28-day regimen of thalidomide, 100 mg by mouth at bedtime, followed by 200 mg for 4 weeks, followed by 300 mg as the final maintenance dose, as tolerated.

Results

Twenty-seven eligible patients (median age 52 years; 52 % appendiceal/48 % colorectal) were enrolled on this trial and included in the analysis, and 26 were evaluable for response. Eighteen patients demonstrated stable disease on adjuvant thalidomide, while eight showed evidence of progression. Approximately 30 % of the patients withdrew due to toxicity. Grade 3/4 toxicities included neurological disorders (16 %), nausea (12 %), vomiting (8 %), and thromboembolism (8 %). Median overall survival (OS) and PFS were 43.0 and 9.3 months, respectively, and median follow-up was 40.4 months. Multivariate modeling showed significant improvements in PFS and OS for appendiceal patients and those with R0 or R1 resections. On an intent-to-treat analysis, the PFS of the study group was 9 months.

Conclusions

Based on these findings, thalidomide cannot be recommended as adjuvant therapy after CS and HIPEC for gastrointestinal malignancies. Further research is needed to identify active agents in this population.     

Phase 2 trial of sorafenib in patients with advanced urothelial cancer

BACKGROUND:

There is no effective second‐line systemic chemotherapy for patients with disease progression after cisplatin‐based chemotherapy. A phase 2 trial of sorafenib was performed to determine the activity and toxicity of this agent in a multi‐institutional setting in patients previously treated with 1 prior chemotherapy regimen.

METHODS:

Twenty‐seven patients with advanced urothelial carcinoma were treated with sorafenib 400 mg orally twice daily continuously until progression or unacceptable toxicity.

RESULTS:

There were no objective responses observed. The 4‐month progression‐free survival (PFS) rate was 9.5%; median overall survival of the group was 6.8 months. There were no therapy‐related deaths, and common grade 3 toxicities included fatigue and hand‐foot syndrome.

CONCLUSIONS:

Although sorafenib as a single agent has minimal activity in patients with advanced urothelial cancer in the second‐line setting, further investigation of tyrosine kinase inhibitors using different trial designs with PFS endpoints is warranted. Cancer 2009. © 2009 American Cancer Society.     

Significance of postoperative CA-125 decline after cytoreductive surgery in stage IIIC/IV ovarian cancer

Objective

The purpose of this study was to evaluate whether the decline in serum CA-125 levels following primary cytoreductive surgery prior to starting adjuvant chemotherapy has a prognostic value in patients with stage IIIC/IV ovarian carcinoma.

Methods

A retrospective review was conducted of all patients with stage IIIC/IV ovarian carcinoma who underwent primary cytoreductive surgery followed by platinum-based chemotherapy from 1994 to 2007. Demographic, pathologic, treatment, and survival data were collected. Patients were included if serum CA-125 levels were drawn preoperatively and within one week prior to their first chemotherapy cycle, and whose postoperative CA-125 level declined. Percentage decline was calculated, and was compared with standard statistical tests in groups by 25% declination intervals.

Results

Of the 112 stage IIIC/IV patients, 81 (72.3%) met the above inclusion criteria. The median time from surgery to postoperative CA-125 sampling was 16 days (range: 7-42). A ≥75% decline was associated with a median progression-free survival (PFS) of 25 months (95% CI=0-63). This was significantly longer when compared with each of the other 25% interval groups. After multivariate analysis, independent prognostic factors included a ≥75% decline in CA-125 levels after surgery and the presence of residual tumor. Age, grade, histology, and preoperative CA-125 levels were not statistically significant factors.

Conclusion

A ≥75% decline in serum CA-125 serum levels from primary cytoreductive surgery to the start of adjuvant chemotherapy has independent prognostic value for PFS in patients with stage IIIC/IV ovarian carcinoma.     

Durable remission with salvage second autotransplants in patients with multiple myeloma

BACKGROUND:

High‐dose chemotherapy with autologous hematopoietic cell transplant (auto‐HCT) has been shown to improve survival in patients with newly diagnosed multiple myeloma. However, the role of salvage auto‐HCT for relapsed patients, particularly in the era of novel therapeutics, is not well defined.

METHODS:

The authors performed a retrospective analysis of all 44 myeloma patients (24 men, 20 women) who received a second auto‐HCT as salvage between January 3, 1992 and November 4, 2008 at The University of Texas MD Anderson Cancer Center.

RESULTS:

Median interval between the first and salvage auto‐HCT was 30 months (range, 2‐78 months). Median age at salvage HCT was 54 years (range, 38‐73 years), and median number of salvage treatment regimens was 2 (range, 0‐5). Eleven (25%) patients had high‐risk chromosomal abnormalities on conventional cytogenetic studies between diagnosis and salvage auto‐HCT. Ten patients (23%) experienced grade 3 or higher nonhematologic toxicity after the salvage auto‐HCT. One patient died within 100 days, for a treatment‐related mortality of 2%. Best responses after salvage chemotherapy + salvage auto‐HCT were as follows: complete response (CR) + near CR, 11%; partial response, 79%; overall response rate, 90%. Eighteen (41%) patients received post auto‐HCT maintenance therapy. Median follow‐up from salvage HCT was 41 months. Kaplan‐Meier estimates of median progression‐free survival (PFS) and overall survival (OS) from time of salvage auto‐HCT were 12.3 and 31.7 months, respectively. Median OS from the time of diagnosis was 75 months. In a fitted Bayesian multivariate model, shorter time to progression after first auto‐HCT, greater number of prior therapies, African American race, and immunoglobulin G subtype were significantly associated with worse OS.

CONCLUSIONS:

In selected myeloma patients, a second auto‐HCT for salvage therapy is well tolerated, with acceptable toxicity. The overall response rate and PFS are comparable to other salvage regimens. Cancer 2012;3549–3555. © 2011 American Cancer Society.     

Tau protein as a potential predictive marker in epithelial ovarian cancer patients treated with paclitaxel/platinum first-line chemotherapy

Background

The aim of the study was to evaluate predictive and prognostic significance of microtubule-associated protein Tau in epithelial ovarian cancer (EOC) patients treated with paclitaxel and platinum-based chemotherapy.

Methods

74 patients with EOC (stage I-IV) who underwent cytoreductive surgery followed by standard paclitaxel/platinum chemotherapy were included in the retrospective analysis. Their formalin-fixed, paraffin-embedded tissue specimens were immunohistochemically stained for Tau protein, using semi-quantitative DAKO test. Tau expression was acknowledged as negative (0 and 1+) or positive (2+ and 3+). The correlation between Tau expression, progression free survival (PFS) and overall survival (OS) was evaluated. Statistical analysis included Kaplan-Meyer estimator, long rank test, Mann Whitney test and Cox proportional hazards model.

Results

25.7% (19/74) and 74.3% (55/74) of the patients were classified as Tau-negative and Tau-positive, respectively. Median PFS was 28.7 months for Tau-negative group and 15.9 months for Tau-positive group (p = 0.0355). In the univariate analysis 3-year OS in Tau-negative and Tau-positive groups was 80.2% and 52.4%, respectively (p = 0.0198). Low expression of protein Tau was associated with better OS, whereas an advanced stage at diagnosis, suboptimal surgery, serous histological type and resistance to first line chemotherapy were each correlated with worse OS (p <0,05). In multivariate analysis only resistance to first line chemotherapy remained significant (HR 22.59; 95% CI, 8.71-58.55; p <0.0001).

Conclusions

Negative tau protein seems to be both good prognostic factor and a predictor of response to paclitaxel/platinum-based chemotherapy in EOC patients.     

Phase II study of Gleevec plus hydroxyurea in adults with progressive or recurrent low-grade glioma

BACKGROUND:

We evaluated the efficacy of imatinib plus hydroxyurea in patients with progressive/recurrent low‐grade glioma.

METHODS:

A total of 64 patients with recurrent/progressive low‐grade glioma were enrolled in this single‐center study that stratified patients into astrocytoma and oligodendroglioma cohorts. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg per day for patients not on enzyme‐inducing antiepileptic drugs (EIAEDs) and at 500 mg twice a day if on EIAEDs. The primary endpoint was progression‐free survival at 12 months (PFS‐12) and secondary endpoints were safety, median progression‐free survival, and radiographic response rate.

RESULTS:

Thirty‐two patients were enrolled into each cohort. Eleven patients (17%) had before radiotherapy and 24 (38%) had received before chemotherapy. The median PFS and PFS‐12 were 11 months and 39%, respectively. Outcome did not differ between the histologic cohorts. No patient achieved a radiographic response. The most common grade 3 or greater adverse events were neutropenia (11%), thrombocytopenia (3%), and diarrhea (3%).

CONCLUSIONS:

Imatinib plus hydroxyurea was well tolerated among recurrent/progressive LGG patients but this regimen demonstrated negligible antitumor activity. Cancer 2012. © 2012 American Cancer Society.     

Chemotherapy with 5-fluorouracil and a platinum compound improves outcomes in metastatic small bowel adenocarcinoma

BACKGROUND.

Metastatic small bowel adenocarcinoma (SBA) has a poor prognosis. Because of the rarity of SBA, only a few studies have evaluated the role of chemotherapy in the treatment of metastatic SBA; thus, the benefit, if any, of adding a platinum compound to fluorouracil (5‐FU) is unknown. The objective of this retrospective study was to determine whether the addition of a platinum compound to 5‐FU provided any benefit in the treatment of patients with metastatic SBA.

METHODS.

The authors identified 80 patients with metastatic SBA who were treated with chemotherapy at the University of Texas M. D. Anderson Cancer Center between 1978 and 2005. Response rates, progression‐free survival (PFS), and overall survival (OS) were compared between patients who received 5‐FU and a platinum compound and patients who received other chemotherapy combinations.

RESULTS.

The median patient age was 53 years. The primary tumor site was the jejunum in 35 patients (43%), duodenum in 30 patients (38%), ileum in 6 patients (8%), and nonspecified small bowel in 9 patients (11%). Of all 80 patients, 29 patients (36%) received 5‐FU and a platinum compound, 41 patients (51%) received 5‐FU without a platinum compound, and 10 patients (13%) received non‐5‐FU–based treatment. Compared with other chemotherapy regimens, treatment with 5‐FU and a platinum agent resulted in a higher response rate (46% vs 16% with other regimens; P = .01) and longer median PFS (8.7 months vs 3.9 months; P ≤ .01) but not better OS (14.8 months vs 12 months; P = .1). In multivariate analysis, treatment with 5‐FU and a platinum compound was a significant predictor of response (odds ratio, 4.5; 95% confidence interval [CI], 1.3‐15.8; P = .02) and PFS (hazard ratio. 0.49; 95% CI, 0.29‐0.84; P = .01) but only reached borderline significance for OS (hazard ratio, 0.63; 95% CI, 0.37‐1.07; P = .08).

CONCLUSIONS.

To the authors' knowledge, the current analysis represents the largest number of patients with metastatic SBA treated with chemotherapy in the literature, and the results suggested that the combination of 5‐FU and a platinum compound leads to a higher response rate and PFS compared with other chemotherapy regimes. The authors concluded that prospective investigation of platinum analogues in the treatment of SBA is warranted. Cancer 2008. © 2008 American Cancer Society.     

Bevacizumab for recurrent alkylator‐refractory anaplastic oligodendroglioma

BACKGROUND:

A retrospective evaluation of single agent bevacizumab was carried out in adults with recurrent alkylator‐refractory 1p19q codeleted anaplastic oligodendrogliomas (AO) with an objective of determining progression‐free survival (PFS). There is no standard therapy for alkylator‐resistant AO, and hence a need exists for new therapies.

METHODS:

Twenty‐two patients aged 24 to 60 years with recurrent AO were treated. All patients had previously been treated with surgery, radiotherapy, adjuvant chemotherapy (temozolomide, 17; carmustine wafers, 4; carmustine, 1), and 1 salvage regimen (procarbazine, lomustine, and vincristine, 15; temozolomide, 6; carmustine wafers, 1). Eleven patients underwent repeat surgery. Patients were treated at second recurrence with bevacizumab, once every 2 weeks, defined as a single cycle. Neurological evaluation was performed every 2 weeks, and neuroradiographic assessment was made after the initial 2 cycles of bevacizumab and subsequently after every 4 cycles of bevacizumab.

RESULTS:

A total of 391 cycles of bevacizumab (median, 14.5 cycles; range, 2‐39 cycles) were administered. Bevacizumab‐related toxicity included fatigue (14 patients; 4 grade 3), leukopenia (9; 1 grade 3), anemia (5; 0 grade 3), hypertension (5; 1 grade 3), deep vein thrombosis (4; 1 grade 3), and wound dehiscence (2; 1 grade 3). Fifteen (68%) patients demonstrated a partial radiographic response, 1 (5.0%) demonstrated stable disease, and 6 (27%) demonstrated progressive disease after 2 cycles of bevacizumab. Time to tumor progression ranged from 1 to 18 months (median, 6.75 months). Survival ranged from 3 to 19 months (median, 8.5 months). Six‐month and 12‐month PFS were 68% and 23%, respectively.

CONCLUSIONS:

Bevacizumab demonstrated efficacy and acceptable toxicity in this cohort of adults with recurrent 1p19q codeleted alkylator‐refractory AO. Cancer 2009. © 2009 American Cancer Society.     

A phase 2 clinical trial of nab‐paclitaxel in previously treated and chemotherapy‐naive patients with metastatic melanoma

BACKGROUND:

nab‐Paclitaxel (ABI‐007, Abraxane), a 130‐nM, albumin‐bound (nab) particle form of Cremophor‐free paclitaxel, is approved for metastatic breast cancer. In the current study, the efficacy and safety of nab‐paclitaxel were evaluated in previously treated and chemotherapy‐naive patients with metastatic melanoma (MM).

METHODS:

Patients with histologically or cytologically confirmed, measurable MM were enrolled. nab‐Paclitaxel was administered intravenously weekly for 3 of 4 weeks at a dose of 100 mg/m² (in previously treated patients) or 150 mg/m² (in chemotherapy‐naive patients).

RESULTS:

Thirty‐seven patients were treated in each cohort. The response rate was 2.7% in the previously treated cohort and 21.6% in the chemotherapy‐naive cohort; the response plus stable disease rate was 37.8% and 48.6% in the previously treated and chemotherapy‐naive cohorts, respectively. The median progression‐free survival (PFS) was 3.5 months and 4.5 months, and the median survival was 12.1 months and 9.6 months, respectively. The probability of being alive and free of disease progression at 6 months was 27% for the previously treated cohort and 34% for the chemotherapy‐naive cohort; the probability of surviving 1 year was 49% and 41%, respectively, for the previously treated and chemotherapy‐naive cohorts. Approximately 78% of the previously treated patients and 49% of the chemotherapy‐naive patients were treated without dose reduction. Eight (22%) chemotherapy‐naive patients discontinued therapy because of toxicities. Drug‐related toxicities included grade 3 to 4 (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]) neuropathy, alopecia, neutropenia, and fatigue.

CONCLUSIONS:

nab‐Paclitaxel was found to be well tolerated and demonstrated activity in both previously treated and chemotherapy‐naive patients with MM. The response rate, PFS, and survival compared favorably with current standard dacarbazine therapy and combination therapies for melanoma. nab‐Paclitaxel therapy of MM should be investigated further in controlled clinical trials. Cancer 2010. © 2010 American Cancer Society.     

Temozolomide for recurrent intracranial supratentorial platinum‐refractory ependymoma

BACKGROUND:

To the authors' knowledge, there currently is no standard therapy for platinum‐resistant ependymoma; hence, a need exists for new therapies. In the current study, a retrospective evaluation of temozolomide (TMZ) in adults with recurrent, supratentorial, platinum‐refractory, World Health Organization grade 2 ependymoma was performed, with an objective of determining 6‐month progression‐free survival (PFS).

METHODS:

A total of 25 patients, ages 28 to 63 years, with recurrent ependymoma were treated. All patients had previously been treated with surgery, radiotherapy, and platinum‐based chemotherapy (cisplatin in 15 patients and carboplatin in 10 patients). Nine patients underwent repeat surgery. Patients were treated at the time of second recurrence with TMZ (5 consecutive days), once every 4 weeks, which was defined as a single cycle. Neurologic evaluation was performed every 4 weeks and neuroradiographic assessment every 8 weeks.

RESULTS:

A total of 68 cycles of TMZ (median, 2 cycles; range, 1‐6 cycles) was administered. TMZ‐related toxicity included leukopenia (7 patients; 1 with grade 3 [grade was determine according to National Cancer Institute Common Toxicity Criteria [version 3.0]), constipation (6 patients; none with grade 3), fatigue (5 patients; none with grade 3), anemia (2; none with grade 3), thrombocytopenia (2; none with grade 3), and deep vein thrombosis (2; none with grade 3). One patient (4%) demonstrated a partial radiographic response, 9 (36%) had stable disease, and 15 (60%) developed progressive disease after 2 cycles of TMZ. Time to tumor progression ranged from 1 to 7 months (median, 2 months). Survival ranged from 2 to 8 months (median, 3 months). The 6‐month and 12‐month PFS were 2% and 0%, respectively.

CONCLUSIONS:

TMZ in this dose schedule demonstrated little efficacy in a cohort of adults with recurrent, intracranial, platinum‐refractory ependymoma. Cancer 2009. © 2009 American Cancer Society.     

The efficacy of taxane chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers

BACKGROUND:

We assessed the efficacy of taxane chemotherapy in BRCA1‐ and BRCA2‐associated patients compared with sporadic metastatic breast cancer patients.

METHODS:

Response rates (RRs) to and progression‐free survival (PFS) after taxane chemotherapy of 35 BRCA1‐associated and 13 BRCA2‐associated metastatic breast cancer patients were compared with those outcomes in 95 matched (1:2) sporadic patients. Matching was performed for age at and year of diagnosis of primary breast cancer, year of metastatic disease, and line of therapy (first vs second or third).

RESULTS:

Among BRCA1‐associated patients, the RR was worse (objective response [OR], 23% vs 38%; progressive disease [PD], 60% vs 19%; P < 0.001); and the median PFS shorter (2.2 vs 4.9 months; P = 0.04) compared with sporadic patients. In the subgroup of hormone receptor (HRec)‐negative patients, BRCA1‐associated patients (n = 20) had a worse RR (OR, 20% vs 42%, respectively; PD, 70% vs 26%, respectively; P = 0.03) and a shorter PFS (1.8 vs 3.8 months; P = 0.004) compared with sporadic patients (n = 19). These outcomes in HRec‐positive patients were similar in BRCA1‐associated (n = 11) and sporadic (n = 61) patients (OR, 36% vs 38%; PD, 28% vs 20%; median PFS, both 5.7 months). In BRCA2‐associated patients, who were mainly HRec‐positive, the OR was higher than in sporadic patients (89% vs 38%, respectively; P = 0.02), whereas the median PFS was not significantly different (7.1 vs 5.7 months, respectively).

CONCLUSIONS:

BRCA1‐associated, HRec‐negative metastatic breast cancer patients were less sensitive to taxane chemotherapy than sporadic HRec‐negative patients. HRec‐positive BRCA1‐ and BRCA2‐associated patients had a sensitivity to taxane chemotherapy similar to that of sporadic patients. Cancer 2012;. © 2011 American Cancer Society.     

Psoas/iliacus muscle invasion from mucinous appendiceal neoplasm. Radiologic appearance and outcome of treatment in 3 patients

Background

Mucinous appendiceal neoplasms have a pattern of metastases that is different from the other gastrointestinal cancers. The first site for cancer dissemination is the peritoneal space surrounding the primary tumor and this is followed by increasingly extensive peritoneal spread. Invasion of the psoas and iliacus muscle is an unusual phenomenon.

Platinum/taxane‐based chemotherapy with or without radiation therapy favorably impacts survival outcomes in stage I uterine papillary serous carcinoma

BACKGROUND:

A study was undertaken to determine recurrence patterns and survival outcomes of stage I uterine papillary serous carcinoma (UPSC) patients.

METHODS:

A retrospective, multi‐institutional study of stage I UPSC patients diagnosed from 1993 to 2006 was performed. Patients underwent comprehensive surgical staging; postoperative treatment included observation (OBS); radiotherapy alone (RT); or platinum/taxane–based chemotherapy (CT) ± RT.

RESULTS:

The authors identified 142 patients with a median follow‐up of 37 months (range, 7‐144 months). Thirty‐three patients were observed, 20 received RT alone, and 89 received CT ± RT. Twenty‐five recurrences (17.6%) were diagnosed, and 60% were extrapelvic. Chemotherapy‐treated patients experienced significantly fewer recurrences than those treated without chemotherapy (P = .013). Specifically, CT ± RT patients had a lower risk of recurrence (11.2%) compared with patients who received RT alone (25%, P = .146) or OBS (30.3%, P = .016). This effect was most pronounced in stage IB/IC (P = .007). CT‐ and CT + RT–treated patients experienced similar recurrence. After multivariate analysis, treatment with chemotherapy was associated with a decreased risk of recurrence (P = .047). The majority of recurrences (88%) were not salvageable. Progression‐free survival (PFS) and cause‐specific survival (CSS) for chemotherapy‐treated patients were more favorable than for those who did not receive chemotherapy (P = .013 and .081). Five‐year PFS and CSS rates were 81.5% and 87.6% in CT ± RT, 64.1% and 59.5% in RT alone, and 64.7% and 70.2% for OBS.

CONCLUSIONS:

Stage I UPSC patients have significant risk for extrapelvic recurrence and poor survival. Recurrence and survival outcomes are improved in well‐staged patients treated with platinum/taxane–based chemotherapy. This multi‐institutional study is the largest to support systemic therapy for early stage UPSC patients. Cancer 2009. © 2009 American Cancer Society.     

Systemic Therapy in Advanced Thymic Epithelial Tumors: Insights from the RYTHMIC Prospective Cohort

Introduction

Thymic epithelial tumors (TETs) are rare malignancies that may be aggressive and difficult to treat. In the advanced setting, systemic treatments may be delivered as primary therapy before surgery or definitive radiotherapy, as exclusive treatment when no focal treatment is feasible, or in the setting of recurrences. Réseau tumeurs THYMIques et Cancer (RYTHMIC) is the nationwide network for TETs in France. The objective of the study was to describe the modalities and analyze the efficacy of systemic treatments for patients with advanced TETs included in the RYTHMIC prospective database hosted by the French Thoracic Cancer Intergroup.

Sunitinib rechallenge in metastatic renal cell carcinoma patients

BACKGROUND:

Sunitinib was a standard initial therapy in metastatic renal cell carcinoma (mRCC). Given the fact that many patients progressed through many available therapies and antitumor activity had been demonstrated with sequential vascular endothelial growth factor‐targeting approaches, a retrospective review was performed of the experience of rechallenge with sunitinib in sunitinib‐refractory mRCC.

METHODS:

mRCC patients who received sunitinib therapy after disease progression on prior sunitinib and other therapy were retrospectively identified. Patient characteristics, toxicity, clinical outcome, Response Evaluation Criteria in Solid Tumors (RECIST) objective response rate, and progression‐free survival (PFS) were recorded.

RESULTS:

Twenty‐three mRCC patients who were rechallenged with sunitinib were identified. Upon rechallenge, 5 patients (22%) achieved an objective partial response. The median PFS with initial treatment was 13.7 months and 7.2 months with rechallenge. Patients with >6‐month interval between sunitinib treatments had a longer PFS with rechallenge than patients who started the rechallenge within 6 months (median PFS, 16.5 vs 6.0 months; P = .03). There was no significant difference in outcome to sunitinib rechallenge based on number or mechanism of intervening treatments. Substantial new toxicity or significantly increased severity of prior toxicity was not seen during rechallenge in this cohort.

CONCLUSIONS:

Sunitinib rechallenge had potential benefits and was tolerated in select metastatic RCC patients. Additional prospective investigation was warranted. Cancer 2010. © 2010 American Cancer Society.