Cisplatin/5-Fluorouracil Treatment of Recurrent Cervical Carcinoma: A Phase II Study with Long-Term Follow-up

doi:10.1006/gyno.1996.0059

Gynecologic Oncology

Volume 60, Issue 3, March 1996, Pages 387-392

https://doi.org/10.1006/gyno.1996.0059 Get rights and content

Abstract

Objective: To evaluate the response rate and corrected survival in patients with recurrent cervical carcinoma (RCC) treated with 100 mg/m²cisplatin (CDDP) iv on Day 1 and 1000 mg/m²5-fluorouracil (5-FU) iv on Days 1 to 5. Methods: A phase II study of CDDP/5-FU in RCC was initiated in 1986. Up to December 1991, a total of 72 patients were enrolled. Of these, 65 were evaluable for response. Results: The overall response rate was 49%. For 9 patients with complete remission, the median duration of response was 16 months, range 6 to 79+. The corresponding figures for 26 patients with partial remission were 10 months, range 3 to 80 months. By multivariate analysis, FIGO stage, disease-free interval, WHO performance status, and number of lesions at recurrence were independent prognostic variables. Twenty-two percent of the patients survived for more than 2 years and 9% for more than 5 years. Toxicity was tolerable. Leucopenia, ototoxicity, and neurotoxicity were the main problems. Conclusion: A high response rate (49%) was observed with CDDP/5-FU treatment in patients with RCC with 9% of the patients surviving for more than 5 years.

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The activity of carboplatin and paclitaxel for recurrent cervical cancer after definitive radiotherapy
2009, Gynecologic Oncology
Citation Excerpt :
The patients in the historical control had been treated with various chemotherapy regimens. As shown in Table 2, before 2005, in our institution, patients with recurrent cervical cancer were treated with platinum-based non-taxane containing regimens, based on previous reports, which showed significant activities in patients with recurrent cervical cancer [17–22]. Each of the chemotherapy cycles was repeated every 3–4 weeks and continued until either disease progression or complete response for a maximum of 9 courses.
The aim of this study was to evaluate the efficacy of paclitaxel–carboplatin (TC) for recurrent cervical cancer after definitive radiotherapy and to compare the results with non-taxane containing platinum-based chemotherapies (NTP).
The records of 59 consecutive women who had undergone salvage chemotherapy with TC (n = 28) or NTP (historical control, n = 31) for recurrence after definitive radiotherapy were retrospectively reviewed. Primary disease and recurrence data was collected. The activity and toxicity of TC were compared with those of NTP. The response rate and progression-free survival (PFS) after recurrence were the main endpoints. Multivariate analysis of prognostic factors for response was performed using the Cox proportional hazards regression model. Survival was calculated using the Kaplan–Meier methods and compared by the log-rank test.
Overall, TC was well tolerated with a response rate of 67.9% (5 CR and 14 PR). The median PFS was 7 months for all patients and 10 months for responders. Myelosuppression was the most common toxicity (grade 3 in 16 patients, grade 4 in 5 patients). On the contrary, NTP showed a response rate of 22.6% with median and mean PFS of 0 month and 2 months, respectively. When compared, TC was significantly superior to NTP with regard to its response rate (p = 0.001) and PFS (p < 0.0001). Moreover, TC showed significantly higher activity in patients with adenocarcinoma histology.
Carboplatin–paclitaxel is active and well tolerated in patients with recurrent cervical cancer after definitive radiotherapy. This combination should be considered as an alternative regimen to cisplatin–paclitaxel in this patient population.
Chemotherapy for recurrent cervical cancer
2008, Cancer Treatment Reviews
Citation Excerpt :
The reported response rate (68%) was impressive. The long-term results of this study demonstrated a response rate of 49% (nine patients achieved complete response).52 In another study the combination of cisplatin (50 mg/m2) with 5-fluoruracil (1000 mg/m2/day, days 1–5) demonstrated a response rate of 21.8% and a median survival of 6.4 months.54
Cervical cancer is the second most common cancer of women worldwide and one of the leading cause of death in relative young women. This review gives an outline of chemotherapy of advanced, persistent or recurrent cervical cancer.
We performed a literature search in the PubMed of almost all relevant articles concerning chemotherapy of advanced, persistent or recurrent cervical cancer.
The available data from the literature is mainly composed of most recent reviews, phase II and randomized phase III clinical trials.
Single-agent cisplatin remains the current standard therapy for advanced, persistent or recurrent cervical cancer. Several single-agents have been tested, but none has been found to be superior compared to cisplatin. Both topotecan and paclitaxel in combination with cisplatin, have yielded superior response rates and progression-free survival without diminishing patient quality of life. However, only the combination of cisplatin and topotecan has improved overall survival. It is important to identify clinical and tumor-related factors predictive of response to cisplatin-based chemotherapy. Future trials are necessary, not only to compare combinations of existing agents, but to incorporate biological agents (monoclonal antibodies or small molecules) to chemotherapy in order to improve the treatment results of advanced, persistent or recurrent cervix cancer.
Chemotherapy for recurrent cervical cancer
2007, Gynecologic Oncology
To give an overview of chemotherapy schemes used in recurrent cervical cancer.
A pubmed search was performed using chemotherapy and recurrent cervical cancer including articles until April 2007.
Most recent articles and articles of interest are discussed.
Single agent cisplatin (50 mg/m²) remains the current standard for recurrent cervical cancer. Numerous chemotherapeutic agents have been tested but did not show convincing evidence of improved survival rates, except for the GOG 179 study which showed an improved survival for the combination of cisplatin and topotecan compared with single agent cisplatin. However, nearly 60% of patients in both groups received prior cisplatinum therapy as a radiosensitizer, which could be responsible for the development of platinum resistance, causing lower response and survival rates in the single platinum group. Hence, the apparent benefit in the doublet group is maybe just a reflection from the change in primary therapy and patient population.
It is hoped that current trials comparing standard therapy with other single or doublet chemotherapeutic regimens or that the use of molecular-targeted agents will give us promising therapeutic options in the future.
Bevacizumab combination therapy in heavily pretreated, recurrent cervical cancer
2006, Gynecologic Oncology
To report the utility of the monoclonal, anti-vascular endothelial growth factor antibody bevacizumab in combination with cytotoxic chemotherapy for women with recurrent cervical cancer.
A retrospective analysis of women with recurrent cervical cancer treated with bevacizumab combination therapy was performed.
Six patients were identified. The patients had a median of 3 prior regimens. All of the patients had multisite, metastatic disease. The combination regimen included IV 5-fluorouracil in 5 (83%) patients and capecitabine in one (17%) subject. Treatment was well tolerated. Grade 4 toxicity occurred in one patient who developed neutropenic sepsis. Clinical benefit (CR, PR, or SD) was noted in 67% of the subjects. This included 1 (17%) complete response, 1 (17%) partial response and two (33%) patients with stable disease. The median time to progression for the four women who demonstrated clinical benefit was 4.3 months.
Combination bevacizumab is well tolerated and displayed encouraging anti-tumor activity in heavily pretreated recurrent cervical cancer.
Phase II trial of capecitabine in recurrent squamous cell carcinoma of the cervix
2005, Gynecologic Oncology
To determine the efficacy and safety of capecitabine in women with inoperable, recurrent, or metastatic squamous cell cervical cancer.
In a phase II IRB approved trial, capecitabine was given at a dosage of 2000 mg/m²/day orally in a divided dose daily for 14 days followed by a 7-day rest period. A standard dose modification scheme was used with one allowed dose reduction or dose escalation. National Cancer Institute criteria for progression, response, and toxicity were utilized. Quality of life data were obtained using the Memorial Symptom Assessment Scale and Functional Assessment for Cancer Therapy, which included a subscale for cervical cancer.
Twenty of 23 enrolled patients were evaluable for response. Stable disease was noted in 5 patients, with a median duration of response of 3.5 months (range, 3–6.5 months). No partial or complete responses were seen. Common grade 3 toxicities were fatigue (30.4%); abdominal pain, constipation, hand–foot syndrome, nausea, and vomiting (8.7% each); as well as dyspnea, headache, and coagulopathy (4.3% each). There were no grade 4 toxicities. All patients with previous exposure to infused 5-FU had evidence of progression. No statistically significant changes in quality of life were noted from baseline to post-cycle 2.
Single-agent capecitabine in patients with recurrent cervical cancer resulted in no objective responses. Although capecitabine is a well-tolerated regimen, as a single agent, it offers minimal benefit in a poor-prognosis cervical cancer population.
Impact of intensity-modulated radiotherapy on acute hematologic toxicity in women with gynecologic malignancies
2002, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
The corresponding rates in women previously treated with WPRT were 42.9%, 14.3%, and 35.6% (10). Many investigators thus routinely administer lower initial CTX doses to these women (11, 16, 17, 31–37). It is possible that IM-WPRT may obviate the need for such dose reductions and thus may improve these patients’ response to salvage therapy.
$Purpose$ : To evaluate the impact of intensity-modulated whole pelvic radiotherapy (IM-WPRT) on acute hematologic toxicity (HT) in gynecology patients.
$Methods and Materials$ : Between February 2000 and June 2001, 36 patients (24 cervix, 12 uterus) received IM-WPRT. The target consisted of the upper vagina, parametria, uterus, and presacral and pelvic lymph nodes. Using commercially available software, seven or nine coplanar IM-WPRT plans were generated. The planning goals were to irradiate the target while minimizing the dose to the small bowel, bladder, and rectum. Pelvic bone marrow (BM) was not a constraint in the planning process. The variables analyzed included white blood count (WBC), absolute neutrophil count (ANC), platelets, and hemoglobin (Hgb) obtained before and weekly during RT. As a comparison, the HT in 88 patients (44 cervix, 44 uterus) treated to the same target volume and total dose (45 Gy) with conventional four-field WPRT was analyzed. In addition, the medullary spaces within the pelvic bones in 10 women were contoured and the average dose-volume histograms representing the pelvic BM were compared between the two groups.
$Results$ : IM-WPRT patients had a lower median age (p = 0.008), higher percentage of squamous histologic features (p = 0.04), and were more likely to receive chemotherapy (CTX) (p = 0.02) than were the WPRT patients. No differences were seen in the baseline WBC, ANC, platelet, or Hgb levels between the two groups. Grade 2 or greater WBC, ANC, and Hgb toxicity was seen in 19.4%, 9.1%, and 8.6% of the IM-WPRT patients, respectively. Comparable rates were seen in the WPRT patients (WBC 21.6%, p = 0.79; ANC 8.3%, p = 0.91; Hgb 9.2%, p = 0.94). No Grade 2 or greater platelet toxicity was seen in either group. Significant HT was infrequent in women treated with RT alone and was comparable in the two groups. In contrast, WPRT + CTX patients experienced more Grade 2 or greater WBC toxicity (60% vs. 31.2%, p = 0.08) and developed lower median WBC (2.8 vs. 3.6 μg/dL, p = 0.05) and ANC (1874 vs. 2669, p = 0.04) nadirs than did IM-WPRT + CTX patients. Moreover, CTX was held more often in the WPRT group secondary to HT (40% vs. 12.5%, p = 0.06). Although Grade 2 or greater ANC (23.5% vs. 15.3%) and Hgb (35.2% vs. 15.2%) toxicity were lower in the IM-WPRT + CTX group, these differences did not reach statistical significance (p = 0.58 and p = 0.22, respectively). The comparison of pelvic BM dose-volume histograms revealed that IM-WPRT planning resulted in significantly less BM volume being irradiated compared with WPRT planning, particularly within the iliac crests.
$Conclusion$ : IM-WPRT has a favorable impact on the risk of acute HT in gynecology patients, particularly in those receiving CTX. Future work is needed to optimize BM sparing in these patients to reduce the risk of significant HT further.

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Regular ArticleCisplatin/5-Fluorouracil Treatment of Recurrent Cervical Carcinoma: A Phase II Study with Long-Term Follow-up

Abstract

Regular Article
Cisplatin/5-Fluorouracil Treatment of Recurrent Cervical Carcinoma: A Phase II Study with Long-Term Follow-up