Dose-dense Neoadjuvant Chemotherapy Research Articles

Dose-Dense Chemotherapy and Neoadjuvant Chemotherapy for Ovarian Cancer

Two of the innovative chemotherapeutic approaches to ovarian cancer treatment, dose-dense chemotherapy and neoadjuvant chemotherapy, will be discussed herein. The primary concept of dose-dense chemotherapy is to administer the same cumulative dose of chemotherapy over a shorter period. Increased dose density is achieved by reducing the interval between each dose of chemotherapy. The Japanese Gynecologic Oncology Group (JGOG) first demonstrated the survival advantage of dose-dense weekly administration of paclitaxel in 2009. However, there are unanswered questions, such as the question of dose-dense carboplatin versus less dose-intensive regimens. Clear cell or mucinous carcinomas seem to need other strategies, such as targeted agents. The aim of neoadjuvant chemotherapy is to reduce tumor volume or spread before main treatment. This could then make the main procedures easier or less invasive, just like breast-conserving surgery after neoadjuvant chemotherapy. In advanced ovarian cancer, standard procedure is maximum primary debulking surgery followed by chemotherapy. Recently, a prospective randomized trial demonstrated that neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to the standard procedure. However, there are several questions that remain unanswered, such as the suitable number of chemotherapy cycles before interval debulking surgery. Some of those questions regarding dose-dense chemotherapy or neoadjuvant chemotherapy may be resolved by ongoing or future prospective trials.

A phase II study of dose-dense neoadjuvant chemotherapy with weekly paclitaxel and carboplatin followed by chemoradiation in locally advanced cervical carcinoma.

5104 Background: We prospectively studied dose dense neoadjuvant chemotherapy (NACT) designed for an enhanced cell kill, better local control and eradication of micrometastases prior to standard concurrent chemoradiation (CRT) in locally advanced cervical cancer. Methods: Between June 2010 and December 2011, 21 patients (median age - 51 years, range 35 - 67) of cervical cancer with locally advanced disease received NACT using paclitaxel (60mg/m2) and carboplatin (AUC-2) weekly for 6 doses. Patients (pts) then received concurrent CRT (external and brachytherapy) with weekly cisplatin (40mg/m2 for 6 doses) at a mean interval of 15 days (range 7–20 days). The primary end-point was response rate i.e. complete response (CR) and partial response (PR) 12 weeks post CRT. Results: Baseline stages were: stage 2A - 19%, 3B - 71.4%, 4A - 9.5%. Squamous cell carcinoma and adenocarcinoma constituted 95.2% and 4.7% pts respectively. Following NACT, 66.6% pts responded (CR -9.5% %; PR – 57.1 %), 23.8% had stable disease (SD) and 4.7% had progressive disease (PD). A total of 18 pts completed NACT and CRT of which 17 were in CR and 1 in PR. One patient with stage 4A disease developed vesicovaginal fistula at end of NACT for which she underwent pelvic exenteration and was in pathological CR. After NACT, one patient developed choroid metastases and was taken off study protocol while another patient was lost to follow up. At a mean follow up 5.8 months (range 1 - 14), 90% pts were in CR, 5% in PR and 5% had PD. During NACT, Grade 3/4 neutropenia, thrombocytopenia and anemia were seen in 33.3%, 4.7% & 9.5% of pts, respectively and grade 3/4 non-hematological toxicities in 9.5% pts. Following CRT, Grade 3/4 neutropenia, thrombocytopenia and anemia were seen in 25%, 5% and 10% of pts, respectively while 20% pts had grade 3/4 non-hematological toxicities. G-CSF was used in 30% pts during NACT and 25% pts during CRT, respectively. Conclusions: NACT with weekly paclitaxel and carboplatin followed by radical CRT is feasible and is associated with a high response rate in locally advanced cervical cancer. This approach needs to be studied in a phase III trial.

Abstract 2707: Long-term significance (15 years) of pathological complete response after dose-dense neo-adjuvant chemotherapy in breast cancer

Abstract Purpose: As a contribution to the discussion of pathological complete response (pCR) as surrogate end-point, after neo-adjuvant chemotherapy (NACT), we studied disease-free survival (DFS) and overall survival (OS) at 15 years with THP-doxorubicin, vinorelbine, 5-Fluorouracil and cyclophosphamide (TNCF regimen). Patients and methods: This retrospective cohort study has been done in 61 patients treated with neo-adjuvant semi-intensive chemotherapy. PCR rate was analysed separately in breast (no histological evidence of invasive tumor cells and / or presence of in situ carcinoma tumor cells) and in nodes (no metastasis). Univariate and multivariate analysis (COX regression) have been used to assess the potential prognostic factors with a median follow up of 13.8 years. Results: Thirty two patients relapsed and 21 died. At 15 years, DFS and OS were 53% and 88% respectively for the patients who achieved pCR compared to 33% and 53% respectively for those who did not achieve pCR. Multivariate analysis with COX model showed that pCR in breast and the number of involved nodes at surgery were 2 factors who can significant predict patients’ DFS and these two factors were significantly related. Conclusion: In this current study, pCR in breast can be used as surrogate marker to predict survival outcome, even with a long-term follow-up of 15 years. When pathological response was incomplete in primary tumor, the number of involved nodes (n > 4 vs n </= 4) significantly predicted survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2707. doi:1538-7445.AM2012-2707

Long-term follow-up of dose-dense neoadjuvant chemotherapy in patients with stage II/III breast cancer.

e11048 Background: Prior studies have shown that women with operable breast cancer had no improvement in disease free survival (DFS) or overall survival (OS) having received chemotherapy (AC) either pre or postoperatively. However, they were able to delineate a subset of women who had improvement in DFS and OS. Achieving a pathological complete remission (pCR) was directly proportional to DFS and OS. Dose dense adjuvant chemotherapy (ATC) has shown a statistically significant improvement in DFS and OS. Methods: We performed a single institution review of patients (pts) enrolled in a neoadjuvant trial who received dose dense neoadjuvant chemotherapy (doxorubicin 60mg/m2 IV Q2wks x4, paclitaxel 175mg/m2IV Q2wks x4 and cyclophosphamide 600 mg/m2 IV Q2wks x4) to asses response rates, safety and DFS. Women with newly diagnosed breast cancer T > 3cm, any N, and M0 were enrolled. Results: Since 2/2003, 48 pts were enrolled in a trial at UAB (mean age 48.7, range 28-64) and received dose dense chemotherapy. The median follow up is 67.9 months (range 8-88 months). Forty one pts completed dose dense chemotherapy and underwent surgery. Seventeen (41.4%) pts achieved a pCR in the breast and of those 14 (34%) pts were also pathologically negative in axillary lymph nodes. Ten of the 17 pts with pCR in the breast were triple negative. Nine pts have had disease relapse including one pt (HER2+) who had achieved a pCR. Two pts had febrile neutropenia, 2 pts had grade 3 anemia and none with grade 4 thrombocytopenia or anemia. Non hematological grade 3 or 4 toxicity included: venous thrombosis 3 pts, hyperglycemia 2 pts, syncope 1 pt, varicella zoster 1 pt and neuropathy in 2 pts. Conclusions: Our results show that dose dense neoadjuvant chemotherapy is effective, achieving high number of pCRs (breast and node) in triple negative and HER2+ breast cancer subtypes as opposed to hormone receptor positive cancers, with tolerable toxicity. Achieving a pCR is an important factor predicting the subsequent risk of relapse across all tumor types. Triple-negative HER2+ ER+ Total Number of cases (%) 17 (41) 6 (15) 18 (44) 41 (100) Breast pCR 10 (59) 5 (29) 2 (12) 17 (100) Breast/node pCR 8 (57) 4 (29) 2 (14) 14 (100) Relapses 4 2* 3 9 pCR in relapses None 1 None 1

Abstract P1-17-03: Comparison of Long Term Outcome of Locally Advanced and Inflammatory Breast Cancers Treated with Dose Dense Neoadjuvant Chemotherapy

Abstract Background: Inflammatory breast cancers (IBC) have a worse prognosis than locally advanced breast cancer (LABC) (KW Hance, JNCI 2005; 97:966-75). We report a series of LABC and IBC treated with dose dense anthracycline and cyclophosphamide and report the correlation between phenotypic features, pathological complete response (pCR) and disease free survival (DFS). Materials and methods: Between 1990 and 2003, 196 patients (pts) with LABC (105 pts) and IBC (91 pts) treated at St Louis hospital received 6 cycles (c) of dose dense Cyclophophamid (1.2g/m2 d1)-Epirubicin (E) (75mg/m2d1) q2w (SIM regimen). 133 patients had frozen biopsy allowing p53 determination. Surgery was done after chemotherapy. pCR was defined as no residual invasive tumor in breast and lymph nodes. Results: Median follow-up was 110 months. IBC were more often ER negative than LABC(52 % vs 34%), more often triple negative (33 % vs 22 %) and more often TP53 mutations .(60% vs 39 %). pCR in breast and lymph nodes was identical in LABC (17 pts,16%) and in IBC (14 pts, 16 %). Table I Pathological response and factors associated with pCR Negative ER and presence of TP53 mutations were strong predictive factors of chemotherapy efficacy in LABC and less in IBCS. histologically grade 3 was not predictive in IBC. Median disease free survival (DFS) was higher in LABC [103 months (m)] than in IBC (54 m), p=.031. Median Overall survival (OS) was not reached in LABC and was of 134 m in IBC (p = .015). A significant effect of ER status on DFS was found in LABC and IBC. When adjusting for ER, IBC still had a significantly shorter DFS (HR 1.64, 95%CI 1.12 to 2.39, P=.011). Similar results were found for OS. For TP 53, a significant interaction was found with LABC/IBC (p=0.017) with a risk for mutated patients in LABC (p=0.004) and a slight and nonsignificant increased risk in IBC patients (p=0.62). Estimated disease free survival at 15 years Conclusion: High risk patients treated with dose dense cyclophosphamide and anthracyclin have very long survival rate. Negativity of ER and p53 mutations are strong predictive factors of good outcome in LABC but less in IBC. This approach in ER-LABC should be prospectively studied.. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-17-03.

Dose-dense chemotherapy in nonmetastatic breast cancer patients: A systematic review and meta-analysis.

645 Background: Dose-dense chemotherapy (DDC) has become the standard of care in the adjuvant setting for women with high-risk breast cancer. We performed a systematic review and meta-analysis of existing data regarding the efficacy and toxicity of DDC approach in nonmetastatic breast cancer. Methods: Relevant RCT's were identified by searching The Cochrane Cancer network register of trials, The Cochrane Library, LILACS and MEDLINE (1.1966 and onwards). The terms adjuvant or neoadjuvant DDC and similar, breast cancer and similar where crossed. Two reviewers independently appraised the quality of trials and extracted data. Results: Eleven trials met the inclusion criteria and were classified into two categories. Three compared DDC to standard schedule. DDC showed superiority in overall survival (OS) and disease free survival (DFS) (HR 0.84; 95% CI 0.72 -0.98, p = 0.03 and HR 0.83 95% CI 0.73-0.94, p = 0.005). No benefit was observed in patients with positive hormonal receptor status. Six trials compared DDC with regimens using standard intervals, but the agents in the 2 arms were not similar nor their dosages. Similar results were obtained for these trials with improvement in OS (HR 0.85; 95% CI 0.75-0.96 p = 0.01) and DFS (HR 0.81; 95% CI 0.73-0.88 p = 0.0003) respectively. Toxicity evaluation depicted a higher non-hematological adverse events rate for DDC arms. One study was included in the systematic review only due to lack of any survival data. Conclusions: Current data indicate a favorable outcome for DDC in OS and DFS. Hormonal receptor status may play a role when using DDC. The acceptance of DDC as standard of care is based upon limited but encouraging data and warrants more randomized controlled trials to further validate this concept. No significant financial relationships to disclose.

Safety and effectiveness of dose dense neoadjuvant chemotherapy in patients with stage II/III breast cancer

e11566 Background: NSABP B-18 randomized women with operable breast cancer to receive chemotherapy (AC) either pre- or postoperatively; in the study there was no significant difference in disease free survival (DFS) or overall survival (OS) among patients in either group. Pathologic complete response rate (pCR) was directly proportional to DFS and OS. Dose dense adjuvant chemotherapy (ATC) has shown a statistically significant improvement in DFS and OS. Methods: We performed a single institution review of pts enrolled in a neoadjuvant trial and who received dose dense neoadjuvant chemotherapy (doxorubicin 60 mg/m2 IV Q2wks x4, paclitaxel 175 mg/m2 IV Q2wks x4, and cyclophosphamide 600 mg/m2 IV Q2wks x4) to assess response rates, safety, and DFS. Women with newly diagnosed breast cancer, T ≥ 3cm, any N, M0 were enrolled. Results: Since 02/2003, 43 pts were enrolled (mean age 47.6, range 28–64) and received dose dense chemotherapy. 41.4% of the pts were triple negative and 14.6% were Her2+ by FISH or IHC. The median follow-up is 49 months (range 8–69). Two patients dropped out without finishing therapy. Forty one pts completed dose dense chemotherapy and proceeded to surgery. 17 pts (41.4%) achieved a pCR in the breast and of those 14 pts were also negative in the axillary lymph nodes (34.1% pCR in the breast and lymph nodes). 10 of the 17 pts with pCR in the breast (8 out of the 14 pts with pCR in breast and axillary lymph nodes) were triple negative. 18 pts (43.9%) achieved PR, 3 pts (7.31%) had SD and 3 pts (7.31%) had PD. Up to November 2008, 7 pts who did not have a pCR have relapsed (4 triple negative, 1 Her2+, 1 ER/PR positive and 1 ER negative, PR positive) with a relapsed free survival rate of 85%. Hematologic toxicity consisted of grade 3 anemia in 2 patients with no grade 4 anemia, no G4 thrombocytopenia and febrile neutropenia in 2 pts. Non-hematologic grade 3 or 4 toxicity consisted of mediport thrombosis in 2 pts, hyperglycemia in 2 pts, syncope in 1 pt, neuropathy in 1 pt, and varicella zoster in 1 pt. Conclusions: Our results show that dose dense neoadjuvant chemotherapy achieves a pCR (breast + node) in about 1/3 of patients (34%) with tolerable toxicity; although the number of patients is limited, our data suggest that triple negative breast cancer seems to be the most sensitive tumor to this regimen. No significant financial relationships to disclose.

The role of preoperative neoadjuvant cytoreductive dose-dense bevacizumab plus docetaxel followed by bevacizumab-doxorubicin-cyclophosphamide regimen in locally advanced operable breast cancer

e11524 Background: Neoadjuvant Rx has been shown to downstage locally advanced breast cancer (LABC) to try to achieve a pathological complete response(PCR) and to convert mastectomy to lumpectomy. Bevacizumab (B) was recently approved to treat metastatic breast cancer in combination with paclitaxel (P). NSABP B-27 used preoperative doxorubicin(A) with cyclophosphamide (C) +- docetaxel (Doc) every 3 wks in primary operable breast cancer, yielding a 12.9% PCR with no residual invasive cancer from AC and 26.1% with the addition of Doc. Based on the success of E2100 with P+B over P, and the more recent AVADO trial showing the superiority of B and Doc over Doc, we have treated such Her2neu-neg pts using Doc/B followed by AC/B with a dose dense every (q) 2 week regimen to see if we could achieve a higher PCR rate and to assess the tolerability of this regimen. Methods: Pts with Her2neu-negative locally advanced operable M0 breast cancer were treated initially with B 10mg/kg iv q 2w with Doc 100mg/m2 q 2w four times with pegfilgrastim given 24 hours after chemotherapy, followed by A 60mg/m2 and C 600mg/m2 q 2 weeks four 4 times with pegfilgrastim given 24 hours after chemotherapy with B 10mg/kg iv for the first AC course as the B was discontinued at least 6 weeks prior to definitive breast surgery. All pts were to get radiation therapy after surgery and appropriate anti-estrogen Rx if estrogen receptor was positive. Results: 15 Her-2 neg women aged 35–61 were treated from 9/06-present for locally advanced primary operable breast cancer. All pts had clinically significant tumor reduction. Of the first 12 post-operative evaluable pts that have completed all the pre- operative therapy, the results showed 5 PCR, including one pt with residual sub-cm DCIS, 7 pathological incomplete responses, yielding a 42% PCR. 3 of the 5 PCR pts had lumpectomies. The major toxicity was excessive eye tearing, nail bed changes and lethargy. Conclusions: This novel dose dense q 2 week regimen is safe, tolerable and effective in LABC with acceptable toxicity. The addition of B to dose dense traditional neoadjuvant chemotherapy seems to increase the PCR. Larger prospective trials using B with dose dense therapy are warranted. No significant financial relationships to disclose.

Randomized study of early intervention compared to standard intervention with darbepoetin-alpha (DA) for chemotherapy-induced anemia (CIA) in early stage breast cancer (ESBC)

19538 Background: Dose dense chemotherapy (DDC) with sequential doxorubicin/ cyclophosphamide followed by paclitaxel Q 14 days has an established place in the treatment of ESBC. However, moderate/severe CIA is a common consequence and therapeutic intervention is frequent. We sought to determine if early intervention at the onset of anemia with DA could reduce the emergence of more severe anemia during therapy and maintain quality of life compared to later intervention. Material and Methods: Non-iron deficient (ferritin > 50) patients (pts) with hemoglobin (Hb) levels >11.0 g/dl scheduled to receive adjuvant or neoadjuvant DDC for ESBC were recruited. Pts were randomly assigned prior to chemotherapy to initiate treatment with DA 200 μg q2w SQ when Hb < 11.5 g/dl (early intervention, EARLY), or DA 200 μg q2w SQ when Hb < 10.0 g/dl (standard intervention, STD) with end of treatment defined as 14 days after the last cycle of chemotherapy. Dose escalation for inadequate response of < 1 g/dl after 6 weeks of DA and dose withholding/reduction for Hb >13 g/dl were pre-specified. Results: The complete sample of 149 pts have been accrued (median age of 53.1, range 28.7 - 74.5). Analysis of fatigue ratings show a trend towards lower fatigue scores in EARLY at Hb nadir, and at end of study,(ANOVA, Group x Time interaction, p=.07). Discussion: Early intervention with DA significantly reduces the risk of developing moderate/severe CIA and increases time spent in the target range during DDC for ESBC. [Table: see text] No significant financial relationships to disclose.

Assessment of pathological complete response (pCR) to neoadjuvant dose-dense chemotherapy in HER2+ patients with locally advanced breast cancer (LABC) treated with trastuzumab (T) compared with HER2+ and HER2- patients treated without T

11057 Purpose: To identify Her2+expression as predictive factor for pCR to T in pts with LABC treated with neoadjuvant chemotherapy. Methods: A total of 127 newly diagnosed stage II-III, including inflammatory tumors, breast cancer pts were reviewed. Median age was 47,7 (r 26,4 - 73,6). Median tumor size was 5 cm (1–10). 57 (44,8%) were T2, 33 (26%) T3 and 37 (29,2%) T4 (25 of them inflammatory). 59 (46,5%) pts were clinically lymph node positive before treatment. 50 pts (39,4%) were hormonal receptor negative, and 38 (30,4%) Her2+. The pts received one of the 2 chemotherapy regimens every 2 weeks with prophylactic growth factors support: A) epirubicin 90 mg/m2-cyclophophamide 600 mg/m2 d1 for 3 cycles, followed by a second sequence with paclitaxel (P) 150 mg/m2- gemcitabine (G) 2500 mg/m2 d1 ± T 2mg/kg/wk according to status Her2 (n= 73); B) adriamicin 40mg/m2 d1 plus P 150mg/m2-G 2000 mg/m2 d2 for 6 cycles (n=54). Subsequently pats underwent surgery and radiotherapy and/or adjuvant hormonal therapy according to institutional practice. Results: 43 (33,9 %) pts achieved a pCR (absence of invasive tumor in the breast). The pts were classified in two groups to analyze the influence of the treatment with T on pCR: (1) Her2+ pats treated with T (20 pts): pCR 50%; (2) The rest of the pts, treated only with chemotherapy (107 pts: 18 Her2+ and 89 Her2- ): pCR 32% (p=0.068). Breast-conserving surgery was performed in 77 pts (60,6%). Conclusions: Both dose dense chemotherapy regimens were highly effective in terms of pCR. Although there were not a significative correlation of Her2+ status and trastuzumab therapy with pCR, probably due to the small number of pts, a favorable tendency was seen in the group of Her2+ tumors treated with T. At the meeting, analysis of the correlation of pCR with progression free survival will be presented. No significant financial relationships to disclose.

Safety and effectiveness of dose dense neoadjuvant chemotherapy in patients with stage II/III breast cancer

10622 Background: NSABP B-18 randomized women with operable breast cancer to receive chemotherapy either pre- or postoperatively; OS and DSF rates at 9 years were identical. Importantly, pathologic complete response (pCR) was directly proportional to DFS and OS. Recently, dose dense adjuvant chemotherapy has shown a statistically significant improvement in DFS and OS. However, no data is available for the use of dose dense preoperative chemotherapy at this time. Methods: Women enrolled in the I-SPY correlative trial with newly diagnosed breast cancer, T ≥ 3cm, any N, M0 were evaluated to assess response rates and safety to dose dense neoadjuvant chemotherapy (doxorubicin 60 mg/m2 IV Q2 wks × 4, paclitaxel 175 mg/m2 IV Q2 wks × 4, and cyclophosphamide 600 mg/m2 IV Q2 wks × 4). Results: Since 02/2003, 43 pts have been treated with dose dense neoadjuvant chemotherapy on the I-SPY trial at UAB (mean age 47.9). 47% of the pts were ER+, 37% were PR+ and 5% were Her2+ by FISH. 2 pts dropped out for personal reasons and 9 pts are actively undergoing treatment. Overall, 32 pts received dose dense chemotherapy and proceeded to surgery. Of those, 31 received dose dense sequential ATC and 1 received dose dense concurrent AC followed by T. 34% had a pCR (breast & nodes) while an additional 10% had a pCR in the breast but residual disease in lymph nodes; 41% had a PR; 9% had SD; and 6% had PD. Hematologic toxicity consisted of grade 3 anemia in 2 pts, febrile neutropenia in 2 pts and no grade 4 thrombocytopenia. Non-hematologic grade 3–4 toxicity consisted of mediport-associated thrombosis in 2 pts, hyperglycemia in 2 pts, syncope in 1 pt, neuropathy in 1 pt, and disseminated varicella in 1 pt. Conclusion: Our results show that dose dense neoadjuvant chemotherapy achieves a pCR (breast & nodes) in about 1/3 of patients (34%) with tolerable toxicity. No significant financial relationships to disclose.

Neoadjuvant, biweekly, dose-dense chemotherapy with epirubicin (E) and cyclophosphamide (C) followed by docetaxel (T) in primary breast cancer (BC)

10656 Background: Primary chemotherapy is established in the treatment of local advanced BC. Two important advances are the chance to detect the clinical responders during the chemotherapy and an increasing rate of breast conserving surgery (BCS). According to the promissing results of dose-dense chemotherapy schedules in the adjuvant setting we tested the benefit of this approach in a primary chemotherapy protocol. Methods: This clinical trial (01/2003–11/2005) enrolled 93 females with advanced (cT2-cT4), non metastatic BC. The pts received four courses of E (90 mg/m2) and C (600 mg/m2) q2w, followed by four courses of T (100/75 mg/m2) q2w. The severe hand-foot-skin reaction NCI-CTG grade 3 during the T courses of the first pts (G1: n = 19) lead to a dose reduction of T to 75 mg/m2 for the following pts (G2: n = 73). During the first four cycles Pegfilgrastim was applied to prevent neutropenic complications. After every two cycles the actual tumor size was measured by clinical and sonographical examination. The clinical and pathological response, the toxicity and the rate of BCS were evaluated. Results: Pathological complete remission (pCR) of the invasive tumors was observed in 7/19 pts (G1) and 17/73 (G2), pathological partial remission (pPR) in 7/19 pts (G1) and 28/73 (G2), minimal response (pMR) in 3/19 pts (G1) and 14/73 (G2), a stable disease in 2/19 pts (G1) and 11/73 (G2). Two pts in group two showed a progressive disease (pPD). Three pts developed neutropenic fever and stopped the chemotherapy after the 5th and 6th cycle, respectively. One patient died after the 8th cycle in neutropenic sepsis. During this trial the main side effect of T was a hand-foot-skin reaction. Conclusions: This neoadjuvant dose-dense chemotherapy is a potent schedule for the treatment of primary BC. Using T with 75 mg/m2 instead of 100 g/m2 is generally better tolerated. The first group of pts treated with T 100 mg/m2 exhibited a higher frequency of pCR (36.8%) compared to the pts treated with 75 mg/m2 (pCR 23.3%), (p = 0.23). But the increased rate of severe side effects lead to an early dose reduction to 75 mg/m2 in this clinical trial.These first promissing results will be improved in an enlarged number of pts. No significant financial relationships to disclose.

581 POSTER Tobacco habit as a risk factor for lung cancer — a study from Eastern India

To evaluate role of dose dense neo-adjuvant chemotherapy (NACT) prior to standard concurrent chemo-radiation (CCRT) in locally advanced cervical cancer.Between June 2010 and December 2011, 28 patients (median age — 51 years, range, 35 to 67 years) with locally advanced cervical cancer received NACT using paclitaxel (60 mg/m2) and carboplatin (AUC-2) weekly for 6 doses. After a mean interval of 15 days (range 7–23 days), the patients then received definitive radiation and concomitant weekly infusion of cisplatin (40 mg/m2 for 6 doses). Response to concurrent chemo-radiation and toxicity were end points.Following NACT, 67.8% of patients responded; complete (CR) — 2(7.1%), Partial (PR) — 17 (60.7%), stable 7 (25.0%) and 2 patients (7.1%) progressed. 24 of 28 patients received CCRT; 23/24 achieved CR. 22 of 23 complete responders continue to be in CR at a median follow-up of 12 months (range, 7 to 24 months). Grade III/IV neutropenia was the main hematological toxicity seen in 28.5% and 29% of patients, respectively during NACT and CCRT.Neoadjuvant chemotherapy with dose dense weekly paclitaxel and carboplatin followed by standard CCRT is a feasible approach and is associated with a high response rate in locally advanced cervical cancer.

Modulation of Peripheral Blood Dendritic Cell and T Regulatory Cell Populations in the Setting of Dose Dense Neoadjuvant Chemotherapy for Breast Cancer Supported by Granulocyte Macrophage-Colony Stimulating Factor

Modulation of Peripheral Blood Dendritic Cell and T Regulatory Cell Populations in the Setting of Dose Dense Neoadjuvant Chemotherapy for Breast Cancer Supported by Granulocyte Macrophage-Colony Stimulating Factor