Phase II study of irinotecan plus doxorubicin for early recurrent or platinum-refractory ovarian cancer: interim analysis

2007 ◽  
Vol 17 (1) ◽  
pp. 159-163 ◽  
Author(s):  
S. Nishimura ◽  
H. Tsuda ◽  
Y. Hashiguchi ◽  
K. Kokawa ◽  
R. Nishimura ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Response ◽  
Interim Analysis ◽  
Phase Ii Study ◽  
Treatment Schedule ◽  
Platinum Sensitive ◽  
Resistant Disease ◽  
Platinum Resistant ◽  
Platinum Refractory ◽  
Grade 3

The aim of this study was to evaluate the efficacy and toxicity of irinotecan and doxorubicin in the treatment of patients with early recurrent or platinum-refractory ovarian cancer. Nineteen woman from five different institutions were treated. Two patients had platinum-refractory cancer, 11 had platinum-resistant disease, and 6 had platinum-sensitive tumors. An intravenous infusion of Irinotecan (50mg/m2) was given on days 1, 8, and 15, while doxorubicin (40mg/m2) was administered as an intravenous bolus on day 3. This treatment schedule was repeated every 4 weeks. Among the 13 patients defined as having platinum-refractory/platinum-resistant disease, 4 patients achieved a clinical response (30.8%, 95% CI: 9.1–61.4), while only one of 6 patients defined as having platinum-sensitive disease achieved a clinical response (16.7%, 95% CI: 0.4–64.1). Leukopenia and neutropenia were the major dose- limiting toxicities. Grade 3 or 4 leukopenia and neutropenia were noted in 24 (48%) and 33 (66%) of the courses, while febrile neutropenia occurred in 2 courses. Five patients (26%) had grade 2 or worse diarrhea during 7 courses. Our data demonstrated that this regimen might be comparable to standard approved agents in patients with early recurrent or platinum refractory ovarian cancer.

Phase II study for the suboptimally debulked advanced ovarian cancer: Intravenous platinum followed by interval debulking surgery and intravenous paclitaxel + intraperitoneal cisplatin (KCOG9812 study)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5576-5576
Author(s):  
H. Tsubamoto ◽  
K. Ito ◽  
Y. Itani ◽  
K. Ito ◽  
T. Iijima ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Stage Iiib ◽  
Hematologic Toxicity ◽  
Treatment Schedule ◽  
Debulking Surgery ◽  
Interval Debulking Surgery ◽  
Grade 3

5576 Background: Intraperitoneral administration (IP) of cisplatin is recommended by National Cancer Institute for the patients with optimally debulked epitherial ovarian cancer (EOC). However, the advantage is not determined for the suboptimally debulked EOC after the initial surgery. We conducted a phase II study of cisplatin IP after the interval debulking surgery (IDS) following 3 cycles of intravenous platinum. Methods: The initial planned sample size was 30. Eligible patients had previously untreated, histologically confirmed EOC or primary peritoneal carcinoma (PPC) of FIGO stage IIIB-IV with suboptimal (> 1 cm) residual disease. Carboplatin AUC 4 iv d1 and cisplatin 50 mg/sqm iv d3 q21d for 3 cycles. After IDS, paclitaxel 175 mg/sqm iv d1 (or paclitaxel 60 mg/sqm iv d1,d8,d15) and cisplatin 75mg/m2 IP q21d for 4 cycles. Primary endpoint was progression-free survival (PFS) and secondary endpoints were overall survival (OS) and toxicity. Results: 33 patients were enrolled since 1998 till 2005. The median age was 55 (range 19–77). ECOG PS 0/1/2 = 33%/36%/31%; stage IIIB/IIIC/IV = 6%/64%/30%; 91% serous papillary histology. Optimal interval debulking surgery was possible in 85%: none (61%), < 1 cm (24%). Grade 3 or 4 (CTCAE ver.3) non-hematologic toxicity was seen in one patient of neurotoxicity. Grade 3 or 4 hematologic toxicities include: neutropenia (37%), infection (4%), thrombocytopenia (11%). 55% were completed the treatment schedule. The reasons for discontinuing were drug resistance (12%), subileus (4%), elevation of serum creatinine (12%), G3 neurotoxicity (4%), IP catheter block (12%) and infection (4%). Primary recurrent sites of total 20 patients before the second line chemotherapy or surgery were peritoneal cavity (30%), distant metastasis (45%), retroperitoneal lymph nodes (15%), and elevation of serum CA125 (10%). Median PFS was 24 months; median overall survival was 48 months; median follow-up was 36 months (range 15–100). Conclusions: This treatment including cisplatin IP after IDS for the patients with the initially suboptimally debulked EOC was feasible, and showed good prognosis with the small number of the intraperitoneal recurrence. [Table: see text]

scholarly journals A Phase II Study of Patupilone (EPO906) in Patients With Platinum-Resistant or Platinum-Refractory Ovarian Cancer

2012 ◽  
Vol 5 (2) ◽  
pp. 53-59 ◽  
Author(s):  
Willem M. Smit ◽  
Jozef Šufliarsky ◽  
Theresa L. Werner ◽  
Don S. Dizon ◽  
Maria Wagnerová ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Platinum Resistant ◽  
Platinum Refractory

scholarly journals Pazopanib and Oral Cyclophosphamide in Women With Platinum-Resistant or -Refractory Epithelial Ovarian Cancer

2020 ◽  
pp. 542-547 ◽  
Author(s):  
Seema Gulia ◽  
Jaya Ghosh ◽  
Jyoti Bajpai ◽  
Sushmita Rath ◽  
Amita Maheshwari ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Disease Progression ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Oral Cyclophosphamide ◽  
Platinum Resistant ◽  
Hand Foot Syndrome ◽  
Platinum Refractory ◽  
Grade 3

PURPOSE Women with recurrent, multiply-treated epithelial ovarian cancer (EOC) have unfavorable prognosis with limited treatment options after failure of platinum-based regimens. We report here a retrospective analysis of women with recurrent, platinum-resistant EOC treated with an oral regimen of pazopanib and cyclophosphamide. PATIENTS AND METHODS Women with recurrent platinum-resistant or -refractory EOC were treated with pazopanib (600 mg orally daily in 2 divided doses, 400 and 200 mg) and cyclophosphamide (50 mg orally daily for 21 days every 28 days) until disease progression or unacceptable toxicity. RESULTS Twenty patients (17 with platinum-resistant and 3 with platinum-refractory disease) were treated between April 2014 and April 2018. Patients had a median age of 52 years (range, 40-60 years) and median of 4 previous lines of chemotherapy (range, 2-8 previous lines), including 3 patients with progressive disease on bevacizumab. Patients received a median of 6 cycles (range, 2-48 cycles) of pazopanib and cyclophosphamide, with best responses of partial response in 9 patients (45%, including 1 of 3 patients treated previously with bevacizumab), stable disease in 6 patients (30%), and disease progression in 5 patients (25%). The median progression-free survival time was 5.5 months, and median overall survival was 9.5 months. Common adverse events (grade 3 or 4) were fatigue (25%), diarrhea (15%), hand-foot syndrome (10%), mucositis (10%), transaminitis (5%), and hypertension (5%). Dose reduction as a result of toxicity was required in 14 patients (70%), and no patient stopped treatment as a result of toxicity. CONCLUSION Pazopanib plus oral cyclophosphamide is a well-tolerated regimen with clinically relevant benefit in patients with platinum-resistant or -refractory EOC.

Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease.

1992 ◽  
Vol 10 (2) ◽  
pp. 243-248 ◽  
Author(s):  
M Markman ◽  
T Hakes ◽  
B Reichman ◽  
J L Lewis ◽  
S Rubin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Bone Marrow ◽  
Single Agent ◽  
Resistant Disease ◽  
Platinum Resistant ◽  
Platinum Refractory ◽  
Previously Treated ◽  
Wbc Count ◽  
Cns Dysfunction ◽  
Dose Reductions

PURPOSE There is a critical need to find new antineoplastic drugs that are active in platinum-refractory ovarian cancer. We conducted a phase II trial of single-agent ifosfamide with mesna uroprotection in patients with ovarian cancer previously treated with an organoplatinum compound to assess its activity in this clinical setting. PATIENTS AND METHODS Ifosfamide (1.0 or 1.2 g/m2/d for 5 days, delivered on a monthly schedule) was administered to the 57 patients entered onto this trial. Dose reductions were permitted for unacceptable toxicities. RESULTS Toxicity included severe bone marrow suppression (WBC count less than 1,000/microL and/or platelet count less than 50,000/microL), renal dysfunction (serum creatinine level greater than 2.0 mg/dL), and reversible CNS dysfunction (disorientation, hallucinations, somnolence, and agitation), which occurred in 20%, 14%, and 12% of patients, respectively. Of 41 patients with strictly defined platinum-refractory ovarian cancer, five (12%) demonstrated a partial (four) or complete (one) response to this treatment program. CONCLUSION Single-agent ifosfamide has modest but unequivocal activity in platinum-resistant ovarian cancer. Further studies of this drug used as a front-line agent along with an organoplatinum compound or as part of a dose-intensification program with bone marrow, peripheral stem cell, or colony-stimulating factor support are indicated. In addition, single-agent ifosfamide is a reasonable standard second-line treatment strategy in appropriately selected patients with platinum-refractory ovarian cancer.

Phase II study of MKC-1 in patients with metastatic or resistant epithelial ovarian cancer or advanced endometrial cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5577-5577 ◽  
Author(s):  
C. Elser ◽  
H. Hirte ◽  
L. Kaizer ◽  
H. Mackay ◽  
S. Bindra ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Gastrointestinal Disorder ◽  
Ca 125 ◽  
Platinum Resistant ◽  
Parallel Group ◽  
Grade 3

5577 Background: MKC-1 is a novel oral cell cycle inhibitor with preclinical activity in xenograft models of human ovarian and endometrial cancers. MKC-1 also reduces pAKT, an attractive target in endometrial cancer due to frequent PTEN mutations. Methods: The objective of this phase II study is to assess the efficacy of MKC-1 in 2 patient (pt) populations: metastatic or recurrent platinum-resistant ovarian cancer (EOC) and advanced endometrial cancer (EC). Three prior lines of treatment were allowed in both groups. A two arm, parallel group multicenter 2-stage design was used. The primary endpoint was tumor response by RECIST or CA-125. MKC-1 125 mg/m2 was administered orally twice daily for 14 days in 28-day cycles. Results: Accrual to stage one is complete with 21 pts in each arm. 19 pts with EOC (median age 56 yrs, range 31–71) and 9 patients with EC (median 63 range 50–74) were available for efficacy. A total of 66 cycles (EOC/EC: 39/27cycles) median 2 per patient (range 1–8) were delivered. 11/4 pts had prior adjuvant CT, 14/10 had prior systemic CT for advanced disease, and 2/6 received prior radiation. In pts with EOC, 7 pts have stable disease (SD), 12 progressive disease (PD), 2 remain on study. Median time to progression is 1.8 months. In pts with EC 4 pts had SD, 5 PD, 6 remain on study. Toxicity data are available in 28 pts (17/11). Most common adverse events (AE) possibly related to MKC-1 were fatigue, nausea, elevated ALT or AST, urine discoloration, anemia, anorexia, elevated AP and gastrointestinal disorder in 55%, 39%, 36%, 24%, 23%, 21%, 21%, and 21 % of cycles respectively. The only possibly related grade 3+ AEs were neutropenia, leucopenia and hyponatremia in 9 %, 3 %, and 2% of cycles. Conclusions: MKC-1 was well tolerated in both patient populations. Single agent MKC-1 has insufficient activity in platinum resistant EOC to warrant further investigation. Updated clinical data for both patient groups will be presented at the meeting. [Table: see text]

Phase II Study of Oxaliplatin in Platinum-Resistant and Refractory Ovarian Cancer: A Gynecologic Group Study

2003 ◽  
Vol 21 (15) ◽  
pp. 2856-2859 ◽  
Author(s):  
Paula M. Fracasso ◽  
John A. Blessing ◽  
Mark A. Morgan ◽  
Anil K. Sood ◽  
James S. Hoffman
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Response Duration ◽  
Complete Response ◽  
Epithelial Ovarian Carcinoma ◽  
Platinum Sensitive ◽  
Platinum Resistant

Purpose: A phase II study was conducted to determine the efficacy of oxaliplatin therapy in patients with platinum-resistant or refractory epithelial ovarian carcinoma. Materials and Methods: Eligible patients were to receive oxaliplatin 130 mg/m2 intravenously over 2 hours, every 21 days, until progression of disease or adverse effects prohibited further therapy. Results: Of 25 patients entered onto the study, 23 were eligible and assessable. There were no patients with complete response. One patient (4.3%) achieved a partial response, with a response duration of 6.4 months. Nine patients (39.1%) experienced stable disease, with a median duration of 5.6+ months (range, 1.8 to 13.1months). The most frequently reported drug-related toxicities were hematologic, gastrointestinal, and neurologic. Conclusion: Oxaliplatin as a single agent has minimal activity in patients with platinum-resistant or refractory ovarian cancer at the dosage and schedule tested. However, future studies of oxaliplatin combined with other active agents in women with platinum-naïve or platinum-sensitive epithelial ovarian carcinoma may be indicated.

Phase II study of oxaliplatin (OXA) and docetaxel (DTX) in recurrent ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5086-5086
Author(s):  
G. Ferrandina ◽  
M. Ludovisi ◽  
G. D’Agostino ◽  
A. Naldini ◽  
D. Lorusso ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Median Duration ◽  
Phase Ii Study ◽  
Stage Iv ◽  
Recurrent Ovarian Cancer ◽  
Figo Stage ◽  
Platinum Sensitive ◽  
Grade 3

5086 Background: We conducted a phase II study to evaluate the efficacy and safety of OXA and DTX in recurrent platinum-sensitive ovarian cancer patients. Methods: Patients received DTX 75 mg/m2 (60-min i.v.) on day 1, followed by OXA 100 mg/ m2 (120-min i.v.) on day 1 every 21 days. Results: Between October 2002 and November 2005, 30 Caucasian patients (median age: 53.5 yrs; range, 31–73) were enrolled; 7 (23.3%) patients had FIGO stage I-II disease, 22 (73.3%) had FIGO stage III, and 1 (3.3%) had FIGO stage IV disease. Sites of relapse were as follows: abdominal 3 (10.0%), pelvis 5 (16.7%), lymph nodes 10 (33.3%), peritoneal 7 (23.3%), lung 1 (3.3%), and mixed 4 (13.3%). The median PFI was 28.5 months (range 13–91). The median CA125 was 182 U/ml (range 21–5,596 U/ml). Of the 30 patients evaluable, 13 (43.3%) had complete responses and 7 (23.3%) had partial responses, for an overall response rate of 66.6%. The median time to response was 9.5 wks (range 5–32) and the median duration of response was 43 wks (range 5–124). 8 (26.7%) patients had stable disease (median duration of stabilization: 26.5 wks, range 12–43). 2 (6.7%) patients progressed while on treatment. An overall clinical benefit was observed in 93.3% of patients. All patients were evaluable for toxicity. A total of 186 courses were given, with a median of 6 cycles per patient (range 2–11). Severe toxicities (Grade 3–4 NCI-CTC) included: neutropenia in 29.4% of cycles; severe anemia and thrombocytopenia were not observed. Grade 3–4 neurotoxicity and alopecia were detected in 2.8% and 22.8% of cycles respectively. Allergic reaction was observed only in one case. Doses were reduced by 20% in 14.0% of cycles. Conclusions: In recurrent platinum-sensitive ovarian cancer patients the OXA/DTX combination is highly active with acceptable toxicity, thus making it an attractive regimen. No significant financial relationships to disclose.

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