Neoadjuvant chemotherapy and vaginal radical trachelectomy for fertility-sparing treatment in women affected by cervical cancer (FIGO stage IB-IIA1).

OBJECTIVES: The aim of the present report is to support the feasibility and the safety of a new fertility-sparing treatment in young women affected by bulky cervical cancer. METHODS: Between February 2007 and October 2010, seven patients presenting large IB-IIA1 tumors (30-45 mm) were scheduled for conservative treatment. All patients underwent neoadjuvant chemotherapy (NACT) followed by laparoscopic pelvic lymphadenectomy and vaginal radical trachelectomy (VRT). RESULTS: One patient presented hematological toxicity during NACT (grade 3). All patients showed complete disappearance of tumor (n=4/7) or partial response (a 50% or more decrease in total tumor size, n=3/7) to neoadjuvant treatment, and they were all treated with pelvic lymphadenectomy and VRT. Additional treatment (interstitial brachytherapy) was offered to only one woman because of a persistent parametrial tumoral lesion. After a mean follow up of 22 months (range 5-49), no relapse was observed. To date, only one woman in our study attempted to conceive and she is currently pregnant. CONCLUSIONS: Neoadjuvant chemotherapy for fertility sparing treatment is an innovative approach which is potentially quite interesting for many young women affected by bulky cervical cancer. These women, i.e. those with tumors larger than 2 cm (2-5 cm), are traditionally not offered fertility sparing treatment, thus the preliminary data we report here might have a promising impact. Nevertheless, for these patients it may be suitable to use the more radical, and time-tested, conservative surgical approach to allow for a complete and conservative excision of the residual tumor after neoadjuvant treatment. Studies with a larger number of patients and adequate follow-up are required to validate this conservative approach and to define clearly the good indications for this treatment.

Comparative Study of Neoadjuvant Chemotherapy With and Without Zometa for Management of Locally Advanced Breast Cancer With Serum VEGF as Primary Endpoint: The NEOZOL Study.

INTRODUCTION: Neoadjuvant chemotherapy has become the treatment of choice for locally advanced breast cancer. Zoledronic acid (ZA) is a bisphosphonate initially used in the treatment of bone metastases because of its antibone resorption effect. Antitumor effects of ZA, including the inhibition of cell adhesion to mineralized bone or the antiangiogenic effect, have been demonstrated. However, the clinical significance of these effects remains to be determined. MATERIALS AND METHODS: We undertook a multicenter open-label randomized trial to analyze the value of adding ZA to neoadjuvant chemotherapy for TNM clinical stage T2/T3 breast cancer. The primary endpoint was the evolution of serum VEGF. RESULTS: The data from 24 patients were included in the ZA group and 26 in the control group. The evolution of serum VEGF was slightly in favor of ZA at 5.5 months (-0.7% vs. +7.5%), without reaching statistical significance (P = .52). The secondary endpoints were the breast conservation rate (higher with ZA; 83.3% vs. 65.4%; P = NS), pathologic complete response (no effect), and circulating tumor cells (odds ratio, 0.68 in favor of ZA; 95% confidence interval, 0.02-24.36). No cases of jaw necrosis or severe renal failure were observed in either group. CONCLUSION: ZA is an antitumor drug of interest because of its multiple effects on tumor biology. Larger trials with longer follow-up that include additional endpoints such as relapse and survival rates would be of interest.

Probable paclitaxel-induced pancreatitis: uncommon case report and literature review.

Acute pancreatitis is an inflammatory disorder of the pancreas characterized by upper abdominal pain, nausea, and vomiting, with elevated serum amylase or lipase. Gallstones and alcohol are the two main etiologies; drug-induced pancreatitis is uncommon. Paclitaxel associated with pancreatitis is very rare and since that time, only seven case reports have been published. We report a case of a 54-year-old female who developed an acute pancreatitis after administration of the first cycle of neoadjuvant chemotherapy with paclitaxel (175 mg/m2 over 3 h) and carboplatin (AUC 6) for ovarian adenocarcinoma. After conservative management, pancreatitis was resolved. The patient received an additional five cycles of carboplatin with no complication. Because Paclitaxel is used in many chemotherapy protocols, it is important for clinicians to be aware that paclitaxel can induce acute pancreatitis, as early diagnosis can be vital.

Treatment of metastatic breast cancer: a large observational study on adherence to French prescribing guidelines and financial cost of the anti-HER2 antibody trastuzumab.

OBJECTIVE: This observational study aimed at analyzing adherence to prescribing guidelines of anti-HER2 monoclonal antibody trastuzumab treatment for metastatic breast cancer. Efficacy and costs were also evaluated. METHODS: The adherence to the trastuzumab treatment plan was analyzed according to both the French postlicensing guidelines published in 2001 and clinical guidelines from the regional cancer network in a cohort of 131 consecutive patients. RESULTS: The level of appropriateness to the molecular target was very high (92% of the patients showed a positive HER2 status, defined as HER2 3+ confirmed by immunohistochemistry or 2+ confirmed by fluorescent in situ hybridization). The treatment plan was made according to the French postlicensing guidelines in 41 patients (31.3%) and to the regional clinical guidelines for 109 patients (83.2%). The main reason for the difference was the type of molecules authorized for combination to trastuzumab. The median overall survival of the studied population was 18.6 months and the median progression-free survival rate was 7.7 months. Up to death or end of the study, the overall cost for the treatment of breast cancer with trastuzumab per patient and per year was 47,832 euro. CONCLUSION: This quite low adherence of clinicians to the French postlicensing guidelines is in contrast with the high level of adherence to the regional clinical guidelines. The reason is that the latter are less rigid about previously received treatments and enlarge the potential associated cytotoxics to vinorelbine. This supports the French National Cancer Institute decision to get expert clinicians involved together with the French agency for sanitary security of health products and the high health authority in a common elaboration of guidelines.

Use of the monoclonal antibody anti-HER2 trastuzumab in the treatment of metastatic breast cancer: a cost-effectiveness analysis.

BACKGROUND: This open controlled prospective study aimed at evaluating the medical and economical impact of first line chemotherapy for metastatic breast cancer (MBC). PATIENTS AND METHODS: Two groups of HER +++ MBC patients were compared: 26 were treated by a combination of trastuzumab and paclitaxel in 4 "prescriber" centers (group A) and 19 patients were treated by any chemotherapy without addition of trastuzumab, in 6 control centers (group B). The cost of chemotherapy and related hospitalizations was taken into account during the first 8 cycles. RESULTS: Forty-five patients, mean age 51 years have been included. The objective response rate was significantly higher in group A (42% vs. 6%, P = 0.036). The median overall survival was 17 months longer in the group A (29 vs. 12 months). The median progression free survival rate was 12.2 months longer in the group A (19 vs. 7 months). The 1-year survival rate was 85% in the group A and 47% in the group B. The mean overall care cost was 33.271 euro per patient in group A versus 11.191 euro per patient in group B. The additional cost per saved year of life expressed as the incremental cost-effectiveness ratio is 15.370 euro 2002. CONCLUSION: The related additional cost seems affordable for an European health care system and justifies the recommendation for its use in the subpopulation overexpressing HER2.

A phase-III trial of doxorubicin and docetaxel versus doxorubicin and paclitaxel in metastatic breast cancer: results of the ERASME 3 study.

PURPOSE: In first-line metastatic breast cancer, both paclitaxel (P)-doxorubicin (A) and docetaxel (D)-doxorubicin (A) combinations have shown superiority over treatments without taxane. The aim of this study was to compare the two combinations. PATIENTS AND METHODS: Chemotherapy-naive (except for adjuvant therapy) metastatic breast cancer patients were randomly assigned to intravenous AD (arm D) or AP (arm P) every 3 weeks for a maximum of four cycles, then four cycles of single agent docetaxel (arm D) or paclitaxel (arm P). Primary endpoint was overall quality of life (QoL) measured by EORTC QLQ-C30 after four courses of doxorubicin-taxane combination. Secondary endpoints were toxicity, overall survival (OS), progression-free survival (PFS), and QoL sub-scores. RESULTS: Between March 2000 and April 2004, 210 patients were randomized: 103 to arm P and 107 to arm D. Patient characteristics were well balanced between arms. After four courses, QoL score differences between groups or compared to baseline scores were not significant. Response rate was 39.6% for AD and 41.8% for AP. After a median follow-up of 50.2 months, median PFS and median OS were 8.7 and 21.4 months in arm D and 8.0 and 27.3 months in arm P (p = 0.977 and 0.081, respectively). Hematological toxicity was significantly more frequent in arm D than in arm P (p < 10(-6)), as well as grades 3-4 asthenia (p = 0.03). Neuropathy occurred more frequently in arm P (p = 0.03). CONCLUSION: In this study, paclitaxel or docetaxel combined with doxorubicin were not significantly different in terms of QoL scores and efficacy, but had different toxicity profiles.

[Clinical effects of new technologies in medical imagery: the example of breast screening]. / Retentissement clinique des nouvelles technologies d'imagerie médicale: l'exemple de la stratégie de dépistage du cancer du sein.

In the frame of cancer screening, we present a new psychological concept elaborated from our clinical practice of women affected by a breast cancer. The experience of these women is different depending on whether the cancer is discovered in an asymptomatic context or not. We introduce the concept of "anticipatrice medicine" in order to define the implication of diagnosis precocity on the therapeutic strategy, because of a modification of some main parameters which make up the ordinary personal concept. These parameters are : the time in which disease anticipates the symptom and the space where the treatment anticipates the disease. We discuss the paradoxical experience of screening which imposes a medical intervention before any symptom that is for the patient to be treated before any feeling of the disease, and to experience the disease through the experience of a treatment. The different elements of this paradoxical experience are successively identified and analysed. Finally we propose four directions of research in the field of interaction between human and medical technologies.

Phase II study of an oxaliplatin/vinorelbine combination in patients with anthracycline- and taxane-pre-treated metastatic breast cancer.

A phase II study was conducted to evaluate the safety and efficacy of an oxaliplatin (OXA)/vinorelbine (VNB) combination in metastatic breast cancer (MBC) patients pre-treated with anthracyclines and taxanes. Patients received OXA at 130 mg/m (2-h i.v.), day 1, and VNB days 1 and 8 at 24-26 mg/m repeated every 3 weeks. Forty-two patients (median age 54; 64% with liver metastasis, 67% taxane resistant/refractory and 38% anthracycline resistant/refractory) were treated. A median of 4 cycles of treatment was given per patient, with 31% receiving 6 or more. Eleven partial responses and 16 patients with stable disease (five lasting more than 4 months) in 41 eligible patients were seen, for an overall response rate of 26.8% (95% confidence interval 14.2-42.9). Median follow-up was 15.9 months (7.2-30.6), median time to progression was 3.4 months and estimated overall survival was 12.7 months (20 events). Thirty-three patients experienced (National Cancer Institute Common Toxicity Criteria version 2) grade 3-4 neutropenia (one case of febrile neutropenia) and three patients had severe constipation requiring hospitalization. Nine patients developed grade 3 OXA-specific neurotoxicity. There were no treatment-related deaths. We conclude that OXA 130 mg/m (day 1) and VNB 24 mg/m (day 1 and 8) combination given every 3 weeks is effective with a good safety profile in MBC patients previously treated with anthracyclines and taxanes.

Epirubicin and paclitaxel (EPI-TAX regimen) for advanced ovarian cancer after failure of platinum-containing regimens.

BACKGROUND: The place of anthracyclines in the treatment of advanced ovarian cancer remains a matter of debate. We have assessed the feasibility and evaluated the tolerance of epirubicin (EPI) combined with paclitaxel (TAX) in heavily pretreated ovarian cancer patients. METHODS: Between March 1996 and March 1998, 34 patients with ovarian cancer in relapse after platinum-based chemotherapy received EPI (75 mg/m(2)/day, iv) and TAX (175 mg/m(2)/day, 3-h infusion). Cycles were repeated every 3 weeks. This treatment was second-line for 10 patients and third/fourth-line for 24. RESULTS: Of the 34 assessable patients, 15 (44%) (95% confidence interval 27-60%) achieved objective response (3 complete and 12 partial responses). The number of previous lines of chemotherapy or previous anthracycline treatments did not influence response rates. Responders to previous paclitaxel-based regimens had a significantly higher response rate to EPI-TAX combination (57%) than nonresponders (11%) (P = 0.05). Median response duration was 40 weeks (range 12-94). Median survival from inclusion was 10.7 months (range 1-40). Myelosuppression was the most frequent side effect. Grade 3/4 neutropenia occurred in 31 patients (91%), febrile neutropenia episodes in 17%, and grade 3/4 anemia and thrombopenia in 27 and 24%, respectively. The main nonhematological toxicities included alopecia and grade 2 peripheral neuropathy (12%). Cardiac dysfunction was observed in one patient after the fourth treatment cycle. CONCLUSIONS: Toxicity of the EPI-TAX regimen was acceptable in this population of heavily pretreated ovarian cancer patients. The regimen was effective and it is considered an option for patients previously responding to paclitaxel-based therapy.