Reduced-Dose Chemotherapy for Breast Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 65+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: City of Hope Medical Center
Disqualifiers: Metastatic disease, Prior chemotherapy, Allergic reactions, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This phase II trial tests how well dose-reduced docetaxel combined with cyclophosphamide works in treating older women with early stage (stage I-III) HER2 negative breast cancer vulnerable to toxicity. Chemotherapy drugs, such as docetaxel and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Docetaxel and cyclophosphamide are commonly used, but is not well tolerated at the standard dose and can affect the way older patients feel physically and emotionally. Giving dose-reduced docetaxel combined with cyclophosphamide may be an effective treatment option and improve quality of life in vulnerable older women with stage I-III HER2 negative breast cancer.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, hormonal therapy should be paused during the study treatment.
What data supports the effectiveness of the drug combination of docetaxel and cyclophosphamide for breast cancer?
Research shows that the combination of docetaxel and cyclophosphamide has been effective in treating metastatic breast cancer, with response rates up to 82% in some studies. This combination has shown promising results in terms of tumor response, although it can cause side effects like neutropenia (a drop in white blood cells that can lead to infection).
12345What safety data exists for reduced-dose chemotherapy using docetaxel and cyclophosphamide in breast cancer treatment?
Docetaxel and cyclophosphamide have been studied for safety in various cancer treatments. Common side effects include neutropenia (low white blood cell count), fluid retention, and skin reactions. Preventive measures like steroids and growth factors can help manage some of these side effects.
16789What makes the reduced-dose chemotherapy with Cyclophosphamide and Docetaxel unique for breast cancer?
This treatment is unique because it uses a combination of two drugs, Cyclophosphamide and Docetaxel, at reduced doses to minimize side effects while maintaining effectiveness. The combination is specifically designed to manage toxicity, such as neutropenia (low white blood cell count), which is a common issue with higher doses of chemotherapy.
124610Eligibility Criteria
This trial is for older women (65+) with early-stage HER2 negative breast cancer who are vulnerable to chemotherapy toxicity. They must have a CARG-BC score of 6 or higher, be able to consent, and willing to answer questionnaires. Excluded are those who've had chemo for their current breast cancer, have recurrent/metastatic disease, or allergies to similar drugs.Inclusion Criteria
Ability to provide informed consent or have a legally authorized representative able to consent on behalf of the patient
For patients with bilateral or multifocal/multicentric breast cancers, specific criteria must be met to enroll
My breast cancer is confirmed HER2-negative and has come back or didn't respond to treatment.
+9 more
Exclusion Criteria
I have been treated with TC for breast cancer before.
I have received chemotherapy for my current breast cancer.
My cancer has returned or spread to other parts of my body.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Patients receive either dose-reduced or standard dose docetaxel and cyclophosphamide intravenously every 21 days for 4 cycles
12 weeks
4 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
2 years
At least 2 visits per year
Participant Groups
The DOROTHY trial is testing a reduced dose of docetaxel combined with cyclophosphamide in treating older women with stage I-III HER2 negative breast cancer. The aim is to see if this lower dose can effectively treat the cancer while improving quality of life by reducing side effects.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm I: (Dose-reduced docetaxel, cyclophosphamide)Experimental Treatment4 Interventions
Patients receive dose-reduced docetaxel IV over 60 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
Group II: Arm II: (Standard dose docetaxel, cyclophosphamide)Active Control4 Interventions
Patients receive standard dose docetaxel IV over 60 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Cytoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇪🇺 Approved in European Union as Endoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇨🇦 Approved in Canada as Neosar for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇯🇵 Approved in Japan as Endoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
City of Hope Medical CenterDuarte, CA
Dana-Farber Cancer InstituteBoston, MA
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Who Is Running the Clinical Trial?
City of Hope Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Docetaxel and cyclophosphamide in patients with advanced solid tumors. [2018]This trial was designed to determine the recommended maximum tolerated dose (MTD), toxicity, pharmacokinetics, and efficacy of docetaxel (Taxotere) and cyclophosphamide (Cytoxan, Neosar) for phase II studies. Both drugs were administered to 39 patients with advanced solid tumors, 26 of whom had breast cancer. Docetaxel doses ranged from 60 to 85 mg/m2 and cyclophosphamide doses ranged from 600 to 800 mg/m2. All patients received steroid prophylaxis. The MTDs for patients with a history of prior chemotherapy were 75 mg/m2 of docetaxel and 700 mg/m2 of cyclophosphamide. For patients with no prior chemotherapy, the MTDs were 75 mg/m2 of docetaxel and 800 mg/m2 of cyclophosphamide. The dose-limiting toxicity was neutropenic fever, observed in 41% of patients and 13% of cycles. Addition of granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]) did not permit further dose escalation, although it did result in briefer periods of neutropenia.
Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. [2018]A pilot phase II study examined the feasibility of 75 mg/m2 of docetaxel (Taxotere) in combination with 50 mg/m2 of doxorubicin and 500 mg/m2 of cyclophosphamide (Cytoxan, Neosar) in the first-line treatment of metastatic breast cancer. This study was designed to evaluate the efficacy and toxicity of the docetaxel/doxorubicin/cyclophosphamide combination both alone and as induction before high-dose chemotherapy, supplemented by autologous peripheral blood stem-cell transplantation. Patients were divided into three groups: one group received 8 courses of docetaxel/doxorubicin/cyclophosphamide; the second received 4 to 6 courses of the same combination with cell sampling, followed by high-dose chemotherapy with autologous peripheral blood stem-cell transplantation; and the third group's regimen was identical to that of the second, with additional granulocyte-colony stimulating factor (G-CSF, filgrastim [Neupogen]). Of 28 patients (149 courses) evaluable for toxicity and response, the overall response rate was 82%, with 5 (18%) complete responses and 18 (64%) partial responses. The most frequent hematologic toxicity was neutropenia; grade 4 neutropenia occurred in 86% of patients, with febrile neutropenia in 9 patients (18%). There was no incidence of infection, possibly because of the administration of oral ciprofloxacin (Cipro) from days 5 to 15 of each cycle. Nonhematologic adverse events were not severe; there was no significant cardiotoxicity. Future randomized trials of docetaxel/doxorubicin/cyclophosphamide as first-line adjuvant therapy of high-risk patients and as induction chemotherapy are in development.
Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. [2018]Preliminary results from phase I trials suggest that the use of docetaxel (Taxotere) and doxorubicin (Adriamycin) is a well tolerated and highly active combination regimen for patients with metastatic breast cancer. The maximum tolerated dose of this combination was 50 mg/m2 of doxorubicin given as an intravenous bolus followed 1 hour later with 75 mg/m2 of docetaxel given as a 1-hour intravenous infusion. Because cardiotoxicity was not observed with this combination, we added cyclophosphamide (Cytoxan, Neosar) in a phase II trial to determine the antitumor activity and tolerability of this 3-drug combination as first-line therapy in patients with metastatic breast cancer. Preliminary results from this study indicate that the Taxotere/ Adriamycin/Cyclophosphamide (TAC) combination produces response rates of up to 80%. However, frequent grade 4 neutropenia was seen in 68% of cycles, febrile neutropenia in 5.5% of cycles, and grade 3 to 4 infection in .8% of cycles. Cardiac toxicity was rare, with 1 case of reversible congestive heart failure (2%), which occurred 2 months after completion of chemotherapy. These preliminary data show that TAC is highly active and that docetaxel did not significantly increase the cardiotoxicity of doxorubicin. Phase III studies in both the first-line and adjuvant settings are warranted.
Combination docetaxel/cyclophosphamide in patients with advanced solid tumors. [2018]Preclinical studies show that docetaxel (Taxotere) and cyclophosphamide (Cytoxan, Neosar) are synergistic against MA 13/C mammary adenocarcinoma. Both agents are highly active as monotherapy in a number of tumors, including metastatic breast cancer. Therefore, we performed a phase I dose-finding study to determine the maximum tolerated dose of this combination regimen in patients with advanced solid tumors. A total of 45 patients were enrolled and received cyclophosphamide followed by docetaxel, both administered as 1-hour intravenous infusions once every 3 weeks. The dose levels of cyclophosphamide/docetaxel were 600/60 mg/m2 (group 0), 600/75 mg/m2 (group I), 700/75 mg/m2 (group 2), 800/75 mg/m2 (group 3), 800/85 mg/m2 (group 4), 800/75 mg/m2 (group 5), and 800/85 mg/m2 (group 6). Patients with dose-limiting neutropenia in groups 5 and 6 received 300 micrograms of granulocyte colony-stimulating factor (G-CSF) (filgrastim [Neupogen]) support on days 2 through 9 during subsequent cycles of chemotherapy. All patients received premedication with 8 mg of dexamethasone twice daily for 5 days, beginning 1 day prior to chemotherapy. The dose-limiting toxicity was neutropenia fever. The recommended dose for phase II studies of cyclophosphamide/docetaxel is 700/75 mg/m2 in previously treated patients and 800/75 mg/m2 in previously untreated patients. G-CSF support did not allow for further dose escalation. Preliminary results from this phase I trial indicate that the combination of docetaxel and cyclophosphamide produced an objective response rate of 69% in 32 patients with metastatic breast cancer (including 3 patients who achieved complete responses).
Docetaxel (Taxotere) plus doxorubicin-based combinations: the evidence of activity in breast cancer. [2018]The high individual response rates of doxorubicin and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) as single agents in breast cancer and their lack of cross-resistance provide the rationale for investigation of the combination of these two uniquely acting agents. A dose-finding study defined the recommended doses for the combination given every 3 weeks as docetaxel 75 mg/m2 plus doxorubicin 50 mg/m2, or docetaxel 60 mg/m2 plus doxorubicin 60 mg/m2. Phase II studies conducted with these doses in first-line treatment of metastatic breast cancer patients resulted in overall response rates ranging between 57% and 77% with long durations of response. The high response rates were maintained in patients with unfavorable prognostic features, such as multiple metastatic disease sites, visceral involvement, and prior exposure to adjuvant chemotherapy. Without prophylactic G-CSF, grade 3/4 neutropenia and febrile neutropenia were the predominant hematologic toxicities. However, infectious complications occurred infrequently. The nonhematologic toxicities of docetaxel and doxorubicin in combination are low in frequency and mild in severity. Additionally, the incidence of congestive heart failure was no greater than that expected with single-agent doxorubicin. The safety and efficacy results of these phase I and II trials appear to be confirmed in a randomized phase III trial comparing docetaxel plus doxorubicin versus doxorubicin plus cyclophosphamide in first-line metastatic breast cancer. Preliminary results reveal a superior overall response rate of 60% with docetaxel plus doxorubicin versus 47% with doxorubicin plus cyclophosphamide (p = .008). Time to disease progression and overall survival results are awaited. The results of these trials, in addition to others being conducted in the adjuvant and the neoadjuvant settings, will establish the ultimate place in therapy for the docetaxel and doxorubicin combination in the management of patients with breast cancer.
Future perspectives of docetaxel (Taxotere) in front-line therapy. [2018]The recognition that early breast cancer is a systemic disease has led to the development of multimodal treatments incorporating adjuvant hormonal and chemotherapies. Adjuvant strategies have improved the outcome of treatment for early breast cancer, but 50% of women still relapse and develop overt metastatic disease, which is largely incurable. In the search for more effective chemotherapies, the taxoid, docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France), has demonstrated high single-agent activity against metastatic breast cancer, including visceral metastases, and is now in phase III trials of combination adjuvant and front-line therapies. When cytotoxic drugs are used in combination, it is important to consider the dose-response relationships and the toxicity profiles of the agents involved. It often is necessary to reduce the doses of drugs given in combination to avoid excessive toxicity; this may result in the administration of suboptimal doses. Early clinical studies have shown that therapeutic doses of docetaxel (60 to 100 mg/m2) can be used in combinations with doxorubicin, 5-fluorouracil, cyclophosphamide, ifosfamide, vinorelbine, and cisplatin. The most frequent adverse effect of docetaxel is neutropenia (91% of patients), but other effects, such as neurosensory changes and fluid retention, also must be taken into consideration when planning combination therapies. It may be possible to ameliorate some toxicities by preventive measures. Fluid retention, which generally occurs at cumulative doses greater than 500 mg/m2, has been shown to be reduced in severity and delayed in onset by prophylactic corticosteroid treatment from the day before each docetaxel administration for 3 to 5 days. Neutropenia may be reduced by treatment with granulocyte colony-stimulating factor, and neurotoxicity may be reduced by protectants such as amifostine. These strategies are under investigation. The high single-agent activity of docetaxel makes it an excellent candidate for treatments such as induction regimens before high-dose chemotherapy and adjuvant therapies. Short-term treatment regimens such as these should also avoid the cumulative toxicities of docetaxel. It is important that new drugs, such as docetaxel, which have shown promising activity against metastatic disease and could have a significant impact on the natural history of early breast cancer, are investigated as front-line treatments.
Presentation and management of docetaxel-related adverse effects in patients with breast cancer. [2022]The taxane chemotherapeutic agent docetaxel has been utilized in the management of breast cancer in the adjuvant, neoadjuvant and metastatic setting. Although well tolerated by the majority of patients, docetaxel toxicity may limit the dose which can be administered. Adverse events include infusion reactions, febrile neutropenia, fatigue, fluid retention, pneumonitis, cutaneous and nail toxicity, epiphora and lacrimal duct stenosis, gastrointestinal complications, and neuropathies. In this review, we explore these complications and how they can be effectively managed to improve patient quality of life during and following docetaxel therapy.
Docetaxel (Taxotere), a review of preclinical and clinical experience. Part II: Clinical experience. [2019]Docetaxel, a promising inhibitor of microtubule depolymerization has shown significant anti-cancer activity during phase I and early phase II trials. The recommended dosage for phase II trials is 100 mg/m2 every 3 weeks which provides optimal activity with tolerable adverse effects. Docetaxel has shown high single agent activity including use as first- or second-line therapy and in anthracycline refractory breast cancer patients. Results have been comparable to that of established treatments for breast cancer. In addition, docetaxel has shown significant activity in non-small cell lung cancer and a range of other tumors, but no activity in renal or colo-rectal tumors. At present it is undergoing further evaluation in combination therapy. The safety profile of docetaxel is well defined. Major adverse effects include hypersensitivity reactions, fluid retention and neutropenia. Peripheral neuropathy is not a significant adverse effect. The aims of phase II trials with regard to counteracting side-effects are therefore 2-fold: firstly, to evaluate the use of premedication with corticosteroids and antihistamines as a means of counteracting hypersensitivity reactions and fluid retention; secondly, to determine whether granulocyte colony stimulating factor may be useful for attenuating neutropenia.
Dose intensity and toxicity associated with Taxotere formulation: a retrospective study in a population of breast cancer patients treated with docetaxel as an adjuvant or neoadjuvant chemotherapy. [2018]Docetaxel is an antineoplastic drug from the taxane family that inhibits tubulin polymerization. Its brand name is Taxotere. In mid-2010, the formulation of Taxotere changed from a two-vial preparation needing a predilution (T2V) to a one-vial ready-to-use preparation (T1V). The aim of this study was to compare the toxicity profile of these two formulations. This retrospective observational and monocentric study included all patients who received Taxotere-based chemotherapy (100 mg/m) as an adjuvant or a neoadjuvant treatment for localized breast cancer, following initial treatment with anthracycline-based chemotherapy. Patients received either T2V or T1V Taxotere depending on the period of treatment. The main endpoint was the ratio of the dose of Taxotere received to that scheduled (R=docetaxel dose received/docetaxel dose scheduled). The secondary endpoint was tolerance. A total of 97 patients were included: 39 in the T2V group and 58 in the T1V group. The ratio of docetaxel received/docetaxel scheduled was significantly lower in the T1V than in the T2V group (0.83 vs. 0.95, respectively; P=0.028). A higher proportion of patients did not receive the totality of the scheduled dose in the T1V than in the T2V group (28 vs. 8%, respectively; P=0.03). Furthermore, the proportion of patients experiencing cutaneous toxicity was significantly higher in the T1V than in the T2V group (50 vs. 15%, respectively; P
Phase I study of docetaxel and cyclophosphamide in patients with advanced or recurrent breast cancer. [2019]A phase I clinical study of combination chemotherapy with docetaxel and cyclophosphamide (CPA) was performed to determine the maximum tolerated dose (MTD), the incidence and severity of toxicities and the pharmacokinetics in patients with advanced or recurrent breast cancer.