A phase II study of neoadjuvant docetaxel plus doxorubicin (KBCS-01) in stage II, III breast cancer

SummaryBackground This multicenter phase II study was conducted to evaluate the response and safety of a combination of docetaxel plus doxorubicin as neoadjuvant therapy for stage II, III breast cancer.Methods Patients with stage II or III breast cancer underwent three cycles of neoadjuvant chemotherapy with doxorubicin 50 mg/m² and docetaxel 75 mg/m² every 3 weeks followed by curative surgery. Prophylactic GCSF was not used.Results Ninety patients were enrolled in the study and 86 were evaluable for efficacy. The median age was 43 years (range, 30–69). The mean relative dose intensity was 0.98 for docetaxel and 0.98 for doxorubicin. Breast-conserving surgery was performed in 12 (13.7%) patients. The clinical overall response rate was 86% and pathologic complete response was 10.5%. Grade 3/4 neutropenia was observed in 26% of total 258 cycles and febrile neutropenia was observed in 15.8%. Pneumonia was observed in one patient and grade 3 mucositis was observed in three patients.Conclusion Docetaxel and doxorubicin was an effective and well-tolerated neoadjuvant chemotherapy for stage II and III breast cancer. Clinical benefit of this treatment will be confirmed by survival data with long term follow up.     

A Phase II Trial of Neoadjuvant Gemcitabine,Epirubicin, and Docetaxel as Primary Treatment of Patients With Locally Advanced or Inflammatory Breast Cancer

BackgroundThree-drug regimens containing gemcitabine, an anthracycline, and a taxane produce response rates of 70%-90% in patients with metastatic breast cancer (MBC) although accompanied by considerable hematologic toxicity. We explored the combination of gemcitabine/epirubicin/docetaxel as neoadjuvant therapy. Docetaxel was administered weekly to decrease myelosuppression.Patients and MethodsA total of 110 patients with locally advanced or inflammatory breast cancer received neoadjuvant gemcitabine 800 mg/m² intravenously (I.V.) days 1 and 8, epirubicin 75 mg/m² I.V. day 1, and docetaxel 30 mg/m² I.V. days 1 and 8, repeated every 21 days for 4 cycles. Then patients had either mastectomy or breast conservation surgery, and pathologic treatment responses were assessed. After surgery, 4 cycles of adjuvant gemcitabine 1000 mg/m² I.V. days 1 and 8 and docetaxel 35 mg/m² I.V. days 1 and 8 were administered at 21-day intervals. After patients completed chemotherapy, locoregional radiation therapy and/or anti-estrogen therapy was administered per standard guidelines.ResultsTreatment with 4 cycles of neoadjuvant gemcitabine, epirubicin, and weekly docetaxel resulted in an objective response in 79 of 110 patients enrolled (72%; 95% CI, 63-80%). Twenty of 103 patients (19%) who had surgery had pathologic complete response (pCR). Moderate hematologic toxicity was evident during neoadjuvant therapy, with grade 3/4 neutropenia in 41% and febrile neutropenia in 11% of the patients. Protocol-specified dose modifications were required in 35% of the patients, and 58% of the patients used myeloid growth factors.ConclusionThe pCR rate of 19% achieved with gemcitabine, epirubicin, and weekly docetaxel confirms previous reports with similar 3-drug regimens. The use of a weekly schedule of docetaxel did not appear to reduce the incidence of grade 3/4 hematologic toxicity.     

A phase II trial of capecitabine and docetaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (FEC) as preoperative treatment in women with stage II/III breast cancer

BackgroundCapecitabine (X) and docetaxel (T) have demonstrated a synergistic effect in preclinical models and a survival benefit in metastatic breast cancer. This study's purpose was to determine the efficacy of X and T followed by 5-fluorouracil/epirubicin/cyclophosphamide (FEC) in the preoperative setting.Patients and methodsPatients with stage II/III breast cancer received four cycles of XT (capecitabine 1650 mg/m² on days 1–14 and docetaxel 60 mg/m² on day 8 every 3 weeks), followed by four cycles of FEC (5-fluorouracil 500 mg/m², epirubicin 90 mg/m², and cyclophosphamide 500 mg/m² on day 1 every 3 weeks). Primary end points were the pathological complete response (pCR) rate and adverse drug reactions.ResultsSeventy-four patients were enrolled and 71 patients were assessable for clinical and pathological responses. The overall response rate was 91.5%. The pCR rate was 14.1% (10 of 71). Grade 3/4 neutropenia was observed in 32.4% of patients. The most common grade 3/4 non-hematologic adverse event was hand–foot syndrome, observed in 11.3% of patients. With 29 months median follow-up, 2-year disease-free survival was estimated 85% for all patients.ConclusionThese data indicate that the sequential combination of XT followed by FEC is a well-tolerated, effective neoadjuvant treatment of stage II/III breast cancer.     

Phase II clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel,associated with trastuzumab,as neoadjuvant treatment in stages II and IIIA HER2-overexpressing breast cancer patients. GEICAM 2003-03 study

Background: We previously reported a phase I trial of liposome-encapsulated doxorubicin citrate (LD), docetaxel and trastuzumab as neoadjuvant in stages II and IIIA human epidermal growth factor receptor 2-overexpressing breast cancer patients. This study evaluates the efficacy of this regimen in a phase II trial.Patients and methods: Patients were treated with LD 50 mg/m² and docetaxel 60 mg/m² every 21days associated with standard trastuzumab dose and pegfilgrastim support.Results: Fifty-nine patients were enrolled; median age: 48 years (range 24–71 years); premenopausal patients: 36 (61%); 19 patients (32%) presented stage IIIA disease and 40 patients (67%) stage II; histological grades 2–3 tumors: 50 patients (84%) and estrogen receptor–progesterone receptor negative: 28 patients (47%). In all, 27% achieved a pathological complete response in breast and axilla (grade 5—Miller and Payne classification); 15% of patients achieved grade 4. Clinical and radiological response rates were 86% and 81%, respectively. Forty-two patients (71%) underwent breast-conserving surgery. The main grades 3–4 toxic effects were non-febrile neutropenia (29%) and fatigue (8%). Grade 2 left ventricular ejection fraction decline was observed in nine patients. No congestive heart failure was observed.Conclusions: LD plus docetaxel combination associated with trastuzumab as neoadjuvant is active in breast cancer and entails a favorable cardiotoxicity profile. This regimen is a new treatment option in these patients.     

A Phase II Trial of Dose-Dense Neoadjuvant Gemcitabine,Epirubicin, and Albumin-Bound Paclitaxel With Pegfilgrastim in the Treatment of Patients With Locally Advanced Breast Cancer

BackgroundNeoadjuvant anthracycline/taxane combinations, with or without gemcitabine, produce pathologic complete responses (pCRs) in 15%-25% of patients. In this multicenter phase II study, we attempted to increase efficacy and decrease toxicity of a 3-drug gemcitabine-containing neoadjuvant regimen by administering dose-dense therapy with pegfilgrastim, and including albumin-bound paclitaxel as the taxane.Patients and MethodsA total of 123 patients with locally advanced breast cancer were enrolled. Patients were treated with 6 doses of neoadjuvant gemcitabine 2000 mg/m², epirubicin 50 mg/m², and albumin-bound paclitaxel 175 mg/m² intravenously administered at 14-day intervals. Following neoadjuvant chemotherapy, patients underwent either mastectomy or breast conservation surgery; pathologic response to treatment was assessed. Postoperatively, patients received 4 doses of gemcitabine 2000 mg/m² with albumin-bound paclitaxel 220 mg/m² at 14-day intervals. Pegfilgrastim 6 mg was administered subcutaneously on day 2 following each dose of chemotherapy.ResultsA total of 116 patients (95%) completed neoadjuvant chemotherapy and had subsequent surgical resection. Twenty-three patients (20%) had a pCR. The estimated 3-year progression-free survival (PFS) and overall survival rates were 48% and 86%, respectively. Neoadjuvant treatment was well tolerated; only 11% of the patients had grade 3/4 neutropenia, with 1 episode of neutropenic fever. Other grade 3/4 toxicities occurred in < 10% of the patients.ConclusionNeoadjuvant biweekly chemotherapy with gemcitabine/epirubicin/albumin-bound paclitaxel with pegfilgrastim is feasible and well tolerated. The pCR rate of 20% and the 3-year PFS rate of 48% are similar to results achieved with other commonly used neoadjuvant regimens.     

Doxorubicin and cyclophosphamide followed by weekly docetaxel as neoadjuvant treatment of early breast cancer: analysis of biological markers in a GEICAM phase II study

Introduction  To evaluate the sequential administration of doxorubicin (A) and cyclophosphamide (C) followed by weekly docetaxel in women with stage II to IIIA breast cancer. Patients and methods  Patients received 60 mg/m² of A and 600 mg/m² of C every three weeks for four cycles followed by 12 infusions of weekly docetaxel at a dose of 36 mg/m² and with a 2-week resting period. Results  Sixty-three women were included. On an intentionto-treat basis, clinical response rate was 90% (95% CI: 83–98), with 46% complete responses. Breast-conserving surgery could be performed in 43 patients (68%). Complete pathological responses in the breast were confirmed in 17% of patients. No correlations between levels of expression of topoisomerase II alpha, survivin or p27 and the pathological response were detected. The study treatment was generally well tolerated. Conclusion  Neoadjuvant AC followed by weekly docetaxel is a feasible regimen for patients with early-stage breast cancer.     

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

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

A multicenter randomized phase II study of sequential epirubicin/cyclophosphamide followed by docetaxel with or without celecoxib or trastuzumab according to HER2 status, as primary chemotherapy for localized invasive breast cancer patients

To assess anti-tumor activity of sequential epirubicin/cyclophosphamide followed by docetaxel with the randomized addition of celecoxib in HER2 negative patients or trastuzumab in HER2 positive patients. From May 2004 till October 2007, 340 patients with stage II and III breast adenocarcinoma, ineligible for breast conserving surgery, received eight sequential three weekly cycles of EC-D [epirubicin (75 mg/m²)–cyclophosphamide (750 mg/m²) for four cycles followed by docetaxel (100 mg/m²) for four cycles]. HER2-negative patients (N = 220) were randomized to receive concomitantly with docetaxel celecoxib 800 mg/day during cycles 5–8 or no additional treatment, while HER2-positive patients confirmed by FISH (N = 120) were randomized to trastuzumab concomitant to docetaxel (8 mg/kg then 6 mg/kg IV every 3 weeks) or no additional preoperative treatment. In the HER2 negative group, pCR (grade 1 and 2 of Chevallier’s classification) was observed in 11.5 and 13% of patients treated without and with neoadjuvant Celecoxib, respectively. In the HER2 positive group, pCR rate reached 26% in those who received neoadjuvant trastuzumab versus 19% in the others. There was no unexpected toxicity, no cardiac toxicity, and no toxic death. Triple negative breast cancers experience the highest pCR rate of 30%. Celecoxib is not likely to improve pCR rates in addition to EC-D in patients with HER2-negative tumor. In HER2-positive tumor patients, trastuzumab added to ECD leads to increased pCR rates. It was the only combination to deserve further study according to the two-stage Fleming’s design used in this trial.     

Response and Prognosis of Docetaxel and Cyclophosphamide as Neoadjuvant Chemotherapy in ER+ HER2− Breast Cancer: A Prospective Phase II Study

BackgroundAlthough a docetaxel and cyclophosphomide (TC) regimen without anthracycline as adjuvant therapy became one of the standard regimens especially for ER-positive (ER⁺)/human epidermal growth factor receptor 2-negative (HER2⁻) primary breast cancer, the efficacy of TC as neoadjuvant chemotherapy (NAC) is not known. We conducted the prospective trial to assess the efficacy of a TC regimen in the neoadjuvant setting for stage II to III ER⁺/HER2⁻ primary breast cancer.Patients and MethodsA TC regimen that included 75 mg/m² of docetaxel and 600 mg/m² of cyclophosphamide for 4 cycles every 3 weeks was administered as NAC. Primary endpoints are the rate of clinical response (clinical partial response and clinical complete response) and pathologic complete response; secondary endpoints are the disease-free survival and overall survival rates.ResultsThirty (71.4%) of 42 tumors had clinical response. No patient achieved pathologic complete response. At the median follow-up period of 105.2 months (range, 12.1-119.7 months), the disease-free survival rate was 81.6%, and the distant disease-free survival rate was 86.8%. In terms of survival, only 1 patient died during the study period. The overall survival rate was 97.4% during the study period. Patients who developed distant recurrence had a trend to have progesterone receptor-negative or weakly positive compared with those who did not develop any recurrence (85.7% vs. 45.2%; P = .05).ConclusionsOur prospective study showed that a TC regimen as NAC achieved a high clinical response rate in stage II to III ER⁺/HER2⁻ breast cancer. A TC regimen without anthracycline as NAC might be one of the options for patients with ER⁺/HER2⁻ breast cancer without high-risk factors including progesterone receptor negativity.     

A phase I trial of gemcitabine, docetaxel and carboplatin administered every 2 weeks as first line treatment in patients with advanced breast cancer

Objective  To determine the maximum tolerated doses (MTDs) and dose limiting toxicities (DLTs) of gemcitabine (GEM), docetaxel (DOC) and carboplatin (CARBO) combination. Patients and methods  A total of 33 previously untreated HER-2 negative patients with stage IIIB-IV breast cancer received escalated doses of GEM, DOC and CARBO all given sequentially on day 1 every 2 weeks. Twenty-three patients (70%) had previously received adjuvant or neoadjuvant chemotherapy. Results  The recommended MTDs are GEM 1,500 mg/m², DOC 50 mg/m² and CARBO 3AUC. Seven dose levels were evaluated and neutropenia was the primary dose-limiting event. Of 319 chemotherapy cycles delivered, grade 3–4 neutropenia occurred in 13.5% of them with two cases of febrile neutropenia. Diarrhea and asthenia were the most common non-hematological toxicities. Three (16%) complete and 6 (32%) partial responses were observed among 19 patients with measurable disease. Conclusion  The biweekly administration of GEM, DOC and CARBO is a well-tolerated regimen which merits further evaluation.     

Neoadjuvant docetaxel followed by adjuvant doxorubicin and cyclophosphamide in patients with stage III breast cancer.

BACKGROUND: To evaluate clinical and pathologic response to neoadjuvant docetaxel therapy in patients with stage III breast cancer. Patients and methods: Forty-five patients were planned to receive four cycles of docetaxel 100 mg/m2 every 3 weeks, followed by surgery, four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (AC) every 3 weeks, radiation therapy (RT), and tamoxifen when indicated. RESULTS: After four cycles of neoadjuvant docetaxel, the clinical response rate within the breast was 59% (95% CI 42% to 73%) and overall (breast and axilla) was 49% (95% CI 38% to 72%) in the intention-to-treat (ITT) population. At the time of surgery, 10% (n=4) of patients had a pathologic complete response (pCR) in the breast, 27% (n=11) had a pCR within the axillary lymph nodes, and 7% (n=3) had a pCR in the breast and axilla (95% CI 2% to 21%). An additional 5% (n=2) had minimal residual invasive tumor (<5 mm). The 5-year overall survival rate was 80%. The percentage of patients with grade 3/4 neutropenia was similar during docetaxel (93%) and AC (86%), while a greater percentage of patients had febrile neutropenia during docetaxel treatment (27%) compared with AC treatment (7%). CONCLUSIONS: Neoadjuvant docetaxel followed by surgery, adjuvant AC, hormonal therapy where indicated, and RT is an active regimen for patients with stage III breast cancer.     

Comparison of 6 cycles versus 4 cycles of neoadjuvant epirubicin plus docetaxel chemotherapy in stages II and III breast cancer

Background

This phase III clinical study was designed to investigate whether 6 cycles of epirubicin plus docetaxel (ED) is more effective than 4 cycles of ED as neoadjuvant chemotherapy (NC) in patients with stage II or III breast cancer.

Patients and methods

Women with breast cancer that had tumors larger than 3 cm were prospectively randomized to receive 4 or 6 cycles of epirubicin 75 mg/m² and docetaxel 75 mg/m² every 3 weeks. The primary end point was the clinical response to NC.

Results

A total of 176 patients were randomly assigned, and 150 patients were assessable for efficacy and toxicity. Groups were well balanced for clinicopathologic parameters. The median age was 42 years (range 30–58). Overall clinical response was observed in 72% with ED4 and 82% with ED6. pCR was observed in 11% with ED4 and in 24% with ED6 (p = 0.047). 47% of the ED4 group underwent breast conserving surgery (BCS) whereas 58% of ED6 group underwent BCS. Grade 3/4 neutropenia was observed in 27% in ED4 and 31% in ED6. Febrile neutropenia occurred in 17% with ED4 and 19% with ED6. Grade 3 mucositis was observed in 8% with ED4 and in 6% with ED6.

Conclusion

Six cycles of ED enhanced the rates of pCR and BCS compared with 4 cycles without increasing treatment-related toxicities.     

Biweekly Administration of Docetaxel and Gemcitabine for Elderly Patients with Advanced Non-Small Cell Lung Cancer: A Phase II Study

Abstract

With 69 years being the median age at diagnosis in the United States, management of elderly patients with advanced non-small cell lung cancer (NSCLC) has become a common problem faced by the oncology practitioner. We evaluated a biweekly administration of the combination regimen using docetaxel (Sanofi Aventis, Athens) and gemcitabine (Eli Lilly, Athens) in a phase II study (objective response rate, median survival, median response duration and safety). A total of 198 cycles were administered to 38 patients with advanced NSCLC with a median age of 72 years (range 65-85 years). Patients received docetaxel 80 mg/m² and gemcitabine 1000 mg/m² on days 1 and 14 of a 28-day cycle. Twenty patients achieved a partial response (PR) (20/34, 58.8%), 4 patients had stable disease (SD) (4/34, 11.7%) and 10 (10/34, 29.4%) had progressive disease (PD). The median time to disease progression was 3 months (range 1-11 months) with a mean survival of 7 months (range 1-29 months). Hematological and non-hematological toxic effects were generally mild to moderate and manageable: grade 3 neurotoxicity and grade 3 allergy occurred in 5 patients (13.1%) and 1 patient (2.6%), respectively. Peripheral neuropathy, mostly grades 1 and 2, was reported in 29 patients (76.3%), which was seen more frequently in patients >70 years of age (P=0.048).

We conclude that the biweekly administration of a docetaxel/gemcitabine combination with G-CSF support constitutes a tolerable and convenient regimen for the treatment of elderly patients with advanced NSCLC, with efficacy similar to that reported in other regimens. Hence, this two-drug combination appears promising and warrants further evaluation.     

Second-line neoadjuvant vinorelbine and gemcitabine combination in locally advanced breast cancer showing no early response to TAC

Due to socioeconomic issues, locally advanced breast cancer (LABC) is still a common presentation of breast cancer in the third world. It was found that LABC patients showing a clinical response after two to four cycles of neoadjuvant chemotherapy have a higher probability of obtaining a pathological complete response at surgery than patients without an early response. In the present work, the short-term effects and toxicity of the neoadjuvant second-line vinorelbine and gemcitabine combination were evaluated in the treatment of LABC who did not show early response to anthracyclines and taxanes-containing regimen. The use of vinorelbine and gemcitabine was based on their use in metastatic breast cancer cases who had been treated before with anthracyclines and taxanes. This was a prospective phase II study accomplished at the Clinical Oncology and Nuclear Medicine Department of Mansoura University, Egypt. Seventy LABC patients not suitable for breast conservative surgery who failed to achieve early response to two cycles of a combination of docetaxel, doxorubicin, and cyclophosphamide (TAC) were treated with a 3-weekly regimen of vinorelbine 30 mg/m² plus gemcitabine 1,200 mg/m² given on days 1 and 8 by intravenous infusion as a second-line neoadjuvant chemotherapy. Response was assessed after the second cycle. Stable and progressed patients were operated upon while responding cases received up to four cycles before the operation. Patient accrual was from June 20, 2007, to October 20, 2009. The objective response was evaluated clinically with breast sonography before every new cycle and before operation while the pathological response was determined postoperatively. The toxicity was evaluated according to the National Cancer Institute––Common Toxicity criteria version 3. The end points of this study were clinical response rate, pathological response rate, and treatment toxicity. Clinical response rate was achieved in 35 cases (50%) while pathological response rate was reported in 4 cases (5.7%). Breast conservative surgery (BCS) became possible in 31 cases (44%). The most common severe toxicities (grades 3 and 4) were neutropenia and thrombocytopenia in 25.7 and 22.8% of cases, respectively. Toxicities were reversible and did not cause death. It is possible to achieve objective clinical and pathological responses of LABC with potentially non-cross-resistant neoadjuvant second-line therapy, leading to BCS in a high proportion of patients. Thus, preoperative second-line chemotherapy appears to be justified when breast conservation is an important treatment goal.     

Gemcitabine plus docetaxel as first-line chemotherapy in patients with advanced non-small cell lung cancer: a lung cancer Galician group phase II study

Background Numerous phase II and III clinical trials have demonstrated a higher activity of combined gemcitabine plus docetaxel schedules against non-small cell lung cancer (NSCLC) than that of both agents in monotherapy. Methods This phase II study evaluated a 3-week based schedule of docetaxel 85 mg/m² (1-h i.v. infusion, d8) combined with gemcitabine 1,000 mg/m² (30-min i.v. infusion; d1,8) as first-line chemotherapy for patients with advanced NSCLC. Results Forty-one patients with non-resectable, stage IIIB/IV, and bidimensionally measurable disease were enrolled. A total of 182 chemotherapy cycles (median 6, range 1–6) was administered to 40 patients during the study; one patient did not receive chemotherapy due to a protocol deviation. Two patients were not evaluable for treatment efficacy. The overall response rate found was 44% (95% CI, 29–59%): three patients (7%) had a complete response and 15 patients (37%) had a partial response (median duration of response = 4.0 months). With a median follow-up of 8.7 months, the median time to disease progression was 4.4 months and the median overall survival was 7.3 months. The combined gemcitabine plus docetaxel chemotherapy was well tolerated except for pulmonary toxicity. The main grade 3–4 hematological toxicity was neutropenia (28% of patients, 9% of cycles). Two cases of febrile neutropenia were reported. The main grade 3–4 non-hematological toxicity was pulmonary toxicity (23% of patients, 6% of cycles). Conclusion Gemcitabine 1,000 mg/m² on days 1 and 8 in combination with docetaxel 85 mg/m² on day 8 given in 3-week cycles is an active and well-tolerated first-line chemotherapeutic regimen for advanced NSCLC.     

Biweekly regimen of cisplatin, gemcitabine and vinorelbine for advanced non-small-cell lung cancer

Purpose: Improving chemotherapeutic efficacy in non-small cell lung cancer (NSCLC) will require the development of new strategies to better use currently available agents. To assess the efficacy and safety of a biweekly regimen of cisplatin, gemcitabine and vinorelbine for advanced non-small-cell lung cancer. Methods: Patients with selected stage IIIb (pleural effusion)/stage IV NSCLC, performance status of 0–2 and normal organ function were eligible. Treatment consisted of cisplatin 100 mg/m² on day 1 plus gemcitabine, 1,000 mg/m² and vinorelbine 25 mg/m² on days 1 and 15 every 28 days. Results: Of the 40 patients enrolled and assessable for response, there were five (12.5%) with confirmed complete response and 14 (35%) with a confirmed partial response for an overall response rate of 47.5%. Nine patients had stable disease while 12 (30%) progressed. Median progression-free survival and overall survival for all patients were 6.3 and 11.1 months, respectively. Toxicity was principally hematologic, with grade 3–4 neutropenia in 30%, and grade 3–4 nausea/vomiting in 22.5%. There were no treatment-related deaths. Conclusions: The biweekly regimen of cisplatin, gemcitabine and vinorelbine is associated with a high rate of response, lesser toxicity than other three-drug regimens and no benefit of survival. Therefore, the regimen under study may be an appealing alternative when considering other treatment modalities for advanced lung cancer, such as neoadjuvant therapy.     

Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate

Docetaxel (Taxotere), alone or in combination with other anticancer agents, has proven efficacy in the first- and second-line treatment of metastatic breast cancer. This phase II study investigated the efficacy and tolerability of docetaxel as neoadjuvant chemotherapy in women with stage II-III primary operable breast cancer. Patients (n=88) were treated with six cycles of docetaxel at 100 mg m(-2) every 21 days, followed by definitive surgery and radiotherapy. After six cycles of docetaxel, the overall clinical response rate was 68.4% (CI 95%: 58.1-78.7%), including 19.0% complete remissions. Breast conservation was achieved in 72.4% of patients. A high pathological complete response (pCR) rate in breast was confirmed in 15 patients (19.8% (CI 95%: 10.8-28.8%)) on Chevallier's classification restricted to breast and in 27 patients (35.5% (CI 95%: 24.7-46.3%)) on Sataloff's classification. After a median follow-up of 30.8 months, 19 recurrences were documented with a median time to first recurrence of 17.3 months. Patients with stage III tumours had more recurrences than patients with stage II tumours (P=0.02). The principal toxicity of docetaxel is myelosuppression and 70.5% of patients developed grade III or IV neutropenia with 13.6% developing neutropenic sepsis. There was no case of severe cardiac toxicity, thrombocytopenia or any other serious adverse events. In conclusion, neoadjuvant docetaxel induces a high pCR and breast-conservation rate. Docetaxel monotherapy is a highly effective regimen that merits formal comparison with currently used combination regimens in a randomised phase III study.     

Monthly docetaxel and weekly gemcitabine in metastatic breast cancer: A?phase II trial

Background:Docetaxel and gemcitabine are active againstbreast cancer. The purpose of this phase II study was to evaluate theefficacy and safety of monthly docetaxel combined with weeklygemcitabine in patients with chemotherapy-pretreated metastatic breastcancer. Patients and methods:Thirty-nine patients were enrolled, ofwhom thirty had received prior chemotherapy in the adjuvant setting,seven for metastatic disease, and two for both, including prioranthracycline in 33 patients. Treatment was gemcitabine 800mg/m² days 1, 8, 15 and docetaxel 100 mg/m² on day1, with cycles repeated every four weeks. Results:Response rate was 79% (95% confidenceinterval (CI): 63%–91%), with 2 complete and 29partial responses. Twenty-five of the responders remainedprogression-free for more than six months. Median survival was 24.5months. Delivered dose intensity of gemcitabine was lower than expected(63% of planned). The predominant hematologic toxicity was grade4 neutropenia in 36 patients, complicated by fever in three patients.With the exception of asthenia, severe non-hematological toxicities wereinfrequent. Conclusions:Monthly docetaxel, combined with weeklygemcitabine, has significant but manageable hematologic toxicity.Despite frequent dose adjustments, this doublet is very active inmetastatic breast cancer, producing a high proportion of durableresponses associated with favorable survival.     

A phase I-II study of gemcitabine and docetaxel in advanced pancreatic cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

Background: Gemcitabine and docetaxel have been claimed to be active single agents in advanced pancreatic cancer. We determined the maximum tolerable dose of docetaxel combined with a weekly fixed dose of gemcitabine and assessed the activity of this combination in advanced pancreatic cancer.Patients and methods: Phase I. Patients were treated with gemcitabine on days 1 and 8, every three weeks, at a fixed dose of 1,000 mg/m²; docetaxel was given at escalating doses starting from 70 mg/m² on day 8. Phase II. In accord with the optimal two-stage phase II study design, 18 patients were treated with gemcitabine (1000 mg/m²) and the maximum tolerable dose of docetaxel (70 mg/m²).Results: Phase I. Dose-limiting toxicities occurred at the second dose level of docetaxel (80 mg/m²), with all three patients developing grades 3 or 4 neutropenia. Consequently, the dose tested in the phase II study was 70 mg/m². Phase II. In the 18 patients enrolled in the study, we registered only one partial response. The time to progression was 3 months, and the median treatment survival was 5.4 months. Grade 3–4 toxicities consisted of neutropenia (three episodes) and thrombocytopenia (two episodes). Furthermore, 10 patients complained of grade 3 fatigue.Conclusions: The addition of docetaxel to gemcitabine does not appear to be useful in advanced pancreatic cancer, since gemcitabine alone achieves similar results.