Chronic Administration of Single-Agent Paclitaxel in Gynecologic Malignancies

doi:10.1006/gyno.2001.6142

Gynecologic Oncology

Volume 81, Issue 2, May 2001, Pages 201-205

https://doi.org/10.1006/gyno.2001.6142 Get rights and content

Abstract

Objective. There are currently limited published data available on the safety and feasibility of the prolonged administration of paclitaxel. The goal of this study was to review the cumulative toxicity associated with the continuous long-term administration of this agent to women with gynecologic cancers.

Methods. Eleven patients with gynecologic malignancies of varying histologic subtypes who received >15 consecutive courses of paclitaxel were identified in a retrospective review of individuals treated between 1994 and 1999 in the Gynecologic Oncology Program of the Cleveland Clinic Taussig Cancer Center. The analysis excluded paclitaxel delivered as a component of an initial chemotherapy regimen for the cancer. Paclitaxel was administered at doses ranging from 80 to 175 mg/m² every 3–4 weeks as a 3-h infusion.

Results. In general, the patients included in this report were heavily pretreated and were continued on therapy either as a result of documentation of an objective response or with evidence of stabilization of disease (e.g., physical examination, radiographic evaluation, CA-125 antigen level) and the maintenance of a satisfactory quality of life. In the 11 patients, the median duration of therapy was 20 cycles (range: 16–36 cycles). Alopecia was observed in all patients. A single patient experienced grade 3 anemia and grade 4 neutropenia. Of note, there was 1 case of grade 2 and no cases of grade 3 peripheral neuropathy in this population.

Conclusion. Prolonged delivery of paclitaxel for >15 consecutive cycles can be safely administered to carefully selected patients with persistent or recurrent advanced gynecologic cancers.

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Cited by (18)

Impact on survival of 12 versus 3 monthly cycles of paclitaxel (175 mg/m<sup>2</sup>) administered to patients with advanced ovarian cancer who attained a complete response to primary platinum-paclitaxel: Follow-up of a Southwest Oncology Group and Gynecologic Oncology Group phase 3 trial
2009, Gynecologic Oncology
Citation Excerpt :
In an effort to improve the survival of women with advanced ovarian cancer who have been shown to be without clinical evidence of disease following the completion of primary platinum-paclitaxel chemotherapy, the Southwest Oncology Group (SWOG) and the Gynecologic Oncology Group (GOG) initiated a randomized phase 3 trial which explored the potential efficacy of administering an additional year (12 monthly cycles) of single agent paclitaxel in this setting [1]. The rationale for this investigative strategy included: (a) potential for clinically-relevant continued tumor cell kill for this known cycle-specific cytotoxic agent [2–4]; (b) theorized anti-angiogenic properties of paclitaxel [5]; (c) demonstrated safety associated with delivery of the agent for > 1 year, with no reports of secondary malignancies or severe organ dysfunction (with the exception of peripheral neuropathy) developing due to “chronic use” [6–8]; and (d) limited retrospective (non-randomized) data suggesting prolonged paclitaxel administration in the second-line setting may be capable of substantially delaying subsequent disease progression for extended periods [6]. When a prospectively defined interim analysis of this study (SWOG-9701/GOG-178) performed upon entry of approximately one-half of the planned patient population revealed “extreme differences” in progression-free survival (PFS) in favor of the administration of 12 monthly cycles of single agent paclitaxel, compared to 3 cycles (median PFS 28 months versus 21 months, p = 0.0023; HR 0.43), the SWOG Data Safety and Monitoring Committee (DSMC) elected to close the trial and inform all patients of the outcome [1].
A SWOG/GOG phase 3 trial exploring the impact of 12-monthly cycles of paclitaxel given to patients with advanced ovarian cancer who achieved a complete response to primary chemotherapy was discontinued by the Data Safety and Monitoring Committee when a prospectively defined interim analysis revealed a highly statistically significant improvement in progression-free survival (PFS). At study closure, it was too early to assess the impact on overall survival.
Patients (n = 296) received either 3 or 12 monthly cycles of paclitaxel (175 mg/m² over 3 h).
Of the 146 patients on the 3-cycle arm, 9 (6%) received > 3 cycles. Median (12 versus 3 cycles; intention-to-treat analysis) updated PFS (all pts) 22 versus 14 months, p = 0.006; overall survival (all pts) 53 versus 48 months, p = 0.34.
Twelve cycles of single agent maintenance paclitaxel significantly improves PFS. Explanations for the lack of a favorable influence on overall survival include: (a) treatment at relapse equalized outcome; (b) the sample size was insufficient to reveal a difference; (c) “crossover” of patients from 3 cycles to longer treatment masked a potential difference. An ongoing phase 3 trial will hopefully provide a definitive answer to the question of the impact of this maintenance strategy on overall survival.
Maintenance therapy in epithelial ovarian cancer: Rationale and results
2008, Clinical Ovarian Cancer
Although ovarian cancer is highly sensitive to chemotherapy, the majority of patients experience recurrence. As a result, it is rational to consider a maintenance strategy to improve overall survival (even if it does not increase the rate of “cure”) and delay the time to symptomatic disease progression. Although a phase III trial of single-agent paclitaxel delivered on a monthly schedule for 12 cycles after the attainment of a clinically defined complete response to primary chemotherapy revealed a substantial improvement in progression-free survival, the effect of this strategy on overall survival remains unresolved. Hopefully, the role of maintenance therapy in patients with ovarian cancer will be defined by ongoing and future trials.
The role of maintenance therapy and novel taxanes in ovarian cancer
2006, Gynecologic Oncology
Despite several studies reporting various degrees of success, the role of maintenance chemotherapy in ovarian cancer remains controversial. This article reviews the available data and the controversy surrounding maintenance therapy. In addition, the role of novel taxanes, which may offer an improved therapeutic index and reduced toxicity relative to conventional therapies in this setting, is discussed.
The available randomized clinical data on extended or maintenance therapy in ovarian cancer are reviewed.
Available data indicate that patients with ovarian cancer undergoing taxane maintenance chemotherapy exhibit a reduced recurrence rate and a longer progression-free survival.
While an additional randomized trial is needed to confirm these benefits and establish maintenance therapy as the standard of care, the authors conclude that maintenance therapy is a valuable option that should be discussed with patients until further data are available. The Gynecologic Oncology Group 212 trial is a randomized clinical trial that is designed to answer whether taxane maintenance therapy offers a survival advantage as well as to determine the impact of such a therapeutic regimen on a patient's quality of life. This trial is also designed to address some of the questions regarding the role of a novel taxane in maintenance therapy in ovarian cancer.
The impact of treatment for gynecological cancer on health-related quality of life (HRQoL): A systematic review
2006, American Journal of Obstetrics and Gynecology
Citation Excerpt :
Seventy-one articles appeared meaningful.27-97 However, 18 articles used their own author-generated or other ad hoc questionnaires.27-44 These scales have not been subjected to standard tests of reliability and validity and therefore do not assess HRQoL reliably.
Gynecologic cancers are major sources of mortality and morbidity. Although many review articles have reported on the impact of these diseases on health-related quality of life (HRQoL), none have reviewed the evidence in specific relation to the effect of treatment on HRQoL. Consequently, we systematically searched 4 electronic databases and hand-searched relevant reference lists and bibliographies to identify literature on this subject. Only 47 studies used a validated questionnaire to measure HRQoL. Although a meta-analysis was not possible, we found HRQoL rarely included as a treatment outcome, and when included assessment was often methodologically flawed. Seldom were pretreatment and posttreatment data collected or treatment regimes documented. Except for a few studies, analysis of HRQoL was conducted on small samples, excluding the cancer site and stage. Consequently, no definitive conclusions could be drawn and therefore we conclude with recommendations for the future reporting of HRQoL in gynecologic oncology studies.
Experience with single-agent paclitaxel consolidation following primary chemotherapy with carboplatin, paclitaxel, and gemcitabine in advanced ovarian cancer
2005, Gynecologic Oncology
Twelve cycles of single-agent paclitaxel have been demonstrated to prolong progression-free survival in women with advanced ovarian cancer whom achieved a clinical complete response to a primary platinum/paclitaxel chemotherapy regimen. This trial was conducted to compare the toxicity and disease-free interval of 3 cycles vs. 12 cycles of paclitaxel consolidation in patients treated with an intensive three-drug front-line regimen of carboplatin, paclitaxel, and gemcitabine.
Following cytoreductive surgery, 26 ovarian cancer patients received primary chemotherapy with carboplatin (AUC = 5, day 1), paclitaxel (175 mg/m² over 1 h, day 1), and gemcitabine (800 mg/m², day 1 day 8), with treatment repeated every 21 days × 6 cycles. The first 13 patients (group A) received three additional cycles of paclitaxel (175 mg/m² over 1 h every 21 days). The second set of 13 patients (group B) also received three cycles of paclitaxel (175 mg/m² over 1 h every 21 days) and then received nine additional cycles of paclitaxel (135 mg/m² over 1 h every 21 days) consolidation therapy. The change from 3 cycles to 12 cycles of consolidation therapy for group B was made following the published results of GOG 178.
In group A, all 13 patients completed three courses of consolidation therapy. One patient experienced grade 3 neutropenia and two patients exhibited both grade 4 neutropenia and thrombocytopenia. Grade ≥2 neuropathy developed in 3 patients (23%). In group B, 9 of the 13 patients whom were intended to receive 12 total cycles of paclitaxel consolidation were able to complete the program. There was no grade 3–4 neutropenia or anemia in this population, although 1 patient developed grade 3 thrombocytopenia. Grade ≥2 neuropathy developed in 7 patients (54%). Although not a randomized experience, median progression-free interval was 76 weeks for group B, and 47 weeks for group A.
Single-agent paclitaxel consolidation therapy can be administered for 12 cycles following first-line carboplatin, paclitaxel, and gemcitabine induction therapy, but there is considerable risk for development of a moderately severe peripheral neuropathy.
A case of chronic paclitaxel administration in ovarian cancer
2003, Gynecologic Oncology
Background. Treatment with chemotherapeutic agents, after initial ovarian tumor debulking, and during recurrence, results in extended chemotherapy. When ovarian cancer recurs, chemotherapy is continued when patients respond to therapy. However, the disease may become stable. Stable disease is clinically relevant and no longer an indication of treatment failure.
Case. A woman with advanced ovarian cancer was treated with cytoxan and cisplatin chemotherapy after having surgical cytoreduction. She progressed and was placed on monthly intravenous paclitaxel. After an initial partial response to therapy, she then went into a prolonged stable course of her disease. She subsequently received 67 cycles of monthly paclitaxel therapy.
Conclusion. Chronic administration of paclitaxel resulted in prolonged stabilization of disease and was well tolerated.

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¹: To whom correspondence and reprint requests should be addressed at Department of Hematology/Medical Oncology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. Fax: (216) 444-9464. E-mail: [email protected].

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Gynecologic Oncology

Abstract

References (20)

A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: a Gynecologic Oncology Group study

Gynecol Oncol

Short-course intravenous prophylaxis for paclitaxel-related hypersensitivity reactions

Ann Oncol

Use of low-dose oral prednisone to prevent paclitaxel-induced arthralgias and myalgias

Gynecol Oncol

Plant antitumor agents. VI. The isolation and structure of paclitaxel, a novel antileukemic and antitumor agent from Taxus brevifolia

J Am Chem Soc

Paclitaxel: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms

Ann Intern Med

Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study

J Clin Oncol

Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer

N Engl J Med

Paclitaxel has moderate activity in squamous cervix cancer: a Gynecologic Oncology Group study

J Clin Oncol

Follow-up of Memorial Sloan-Kettering Cancer Center patients treated on National Cancer Institute treatment of Referral Center Protocol 9103: paclitaxel in refractory ovarian cancer

J Clin Oncol

Cited by (18)

Impact on survival of 12 versus 3 monthly cycles of paclitaxel (175 mg/m<sup>2</sup>) administered to patients with advanced ovarian cancer who attained a complete response to primary platinum-paclitaxel: Follow-up of a Southwest Oncology Group and Gynecologic Oncology Group phase 3 trial

Maintenance therapy in epithelial ovarian cancer: Rationale and results

The role of maintenance therapy and novel taxanes in ovarian cancer

The impact of treatment for gynecological cancer on health-related quality of life (HRQoL): A systematic review

Experience with single-agent paclitaxel consolidation following primary chemotherapy with carboplatin, paclitaxel, and gemcitabine in advanced ovarian cancer

A case of chronic paclitaxel administration in ovarian cancer

Regular ArticleChronic Administration of Single-Agent Paclitaxel in Gynecologic Malignancies

Abstract

Gynecol Oncol

Ann Oncol

Gynecol Oncol

Plant antitumor agents. VI. The isolation and structure of paclitaxel, a novel antileukemic and antitumor agent from Taxus brevifolia

J Am Chem Soc

Paclitaxel: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms

Ann Intern Med

Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study

J Clin Oncol

Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer

N Engl J Med

Paclitaxel has moderate activity in squamous cervix cancer: a Gynecologic Oncology Group study

J Clin Oncol

Follow-up of Memorial Sloan-Kettering Cancer Center patients treated on National Cancer Institute treatment of Referral Center Protocol 9103: paclitaxel in refractory ovarian cancer

J Clin Oncol

Regular Article
Chronic Administration of Single-Agent Paclitaxel in Gynecologic Malignancies