paywalled: Long-term survival in patients with clear cell adenocarcinoma of ovary treated with irinotecan hydrochloride plus cisplatin therapy as first-line

Long-term survival in patients with clear cell adenocarcinoma of ovary treated with irinotecan hydrochloride plus cisplatin therapy as first-line chemotherapy

Article first published online: 28 MAY 2012

DOI: 10.1111/j.1447-0756.2012.01884.x

© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology

Issue

Journal of Obstetrics and Gynaecology Research

Early View (Online Version of Record published before inclusion in an issue)

Abstract

Aim:  Several previous reports showed that irinotecan hydrochloride plus cisplatin (CPT-P) was a candidate first-line chemotherapy regimen for clear cell adenocarcinoma of the ovary (CCC). However, long-term survival in CCC patients treated with CPT-P as first-line chemotherapy remains to be determined. The aim of the present study was to evaluate the long-term results of CPT-P as first-line chemotherapy for CCC.

Material and Methods:  We performed a retrospective review of 31 patients with CCC who were treated with CPT-P between 1996 and 2004.

Results:  The median follow-up period was 91 months.........

Conclusion:  The long-term results suggest CPT-P as a candidate in first-line chemotherapy for CCC in not only stage I, but also in optimally debulked stage II-IV patients with pT1/pT2 disease.

paywalled: Science behind cisplatin-induced nephrotoxicity in humans: A clinical study

Science behind cisplatin-induced nephrotoxicity in humans: A clinical study: Publication year: 2012



Objective To investigate the relationship between serum electrolyte changes and cisplatin induced nephrotoxicity.


Conclusions The present study demonstrates that, acute nephrotoxicity was observed in patients with different types of cancers undergoing cisplatin based chemotherapy due to electrolyte disturbances, when no corrective measures were initiated.

abstract: Regimens with intraperitoneal cisplatin plus intravenuous cyclophosphamide and intraperitoneal carboplatin plus intravenuous cyclophosphamide are equally effective in second line intraperitoneal chemotherapy for advanced ovarian cancer.

Regimens with intraperitoneal cisplatin plus intravenuous cyclophosphamide and intraperitoneal carboplatin plus intravenuous cyclophosphamide are equally effective in second line intraperitoneal chemotherapy for advanced ovarian cancer.:


Abstract
Purpose:
We compared response, survival and side effects of regiments with intravenous cyclophosphamide followed by intraperitoneal cisplatin versus intravenous cyclophosphamide followed by intraperitoneal carboplatin as second line treatment in one center retrospective study.

Material and Methods:
Inclusion criteria were: relapse or recurrence of the disease after surgery and first line treatment; stage III histologicaly documented serous epithelial ovarian cancer after one or more prior regiments of chemotherapy. Recurrence were confirmed throughout restaging laparotomy or second look laparotomy. Patients from one of the groups received 90mg/m2 cisplatin on the first day and 750mg/m2 cyclophosphamide intravenously, while the second group members AUC 6 carboplatin intraperitoneally and 750mg/m2 cyclophosphamide intravenously. Four courses were administrated for each patient.

Results: 

Of the 49 patients in the cisplatin group the response rates were 21 (43%), 10 (20%) and 18 (37%) in the groups of pathologic complete response, pathologic partial response and progressive disease, respectively. The median survival from the initiation of intraperitoneal chemotherapy was 59 months.

Of the 25 patients in the carboplatin group the response rates were 10 (40%), 4 (16%) and 11 (44%) respectively. The median survival -51 months.

The differences between the groups were not statistically significant p 0.05 either in response or in toxicity.

Conclusions: 
The results of our research including relatively long survival from intraperotoneal chemotherapy initiation confirm that carboplatin treatment is as good as cisplatin in second line intraperitoneal chemotherapy for ovarian cancer.

abstract: Phase I trial of intraperitoneal pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer.

Phase I trial of intraperitoneal pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer.

Abstract

PURPOSE:

This phase I trial evaluated intraperitoneal (IP) pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer.

abstract: Vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin, and etoposide (VPCBAE) in the management of three patients with small-cell carcinoma of the ovary

Vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin, and etoposide (VPCBAE) in the management of three patients with small-cell carcinoma of the ovary: Publication year: 2012
Source: Gynecologic Oncology Case Reports, Available online 13 February 2012
abstract

Highlights

► Ovarian small-cell carcinoma of the hypercalcemic type is a rare neoplasm with no standard treatment.
► The chemotherapy regimen including vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin and etoposide (VPCBAE) is safe and effective.has limited toxicities and was effective in the 3 patients described in this case report.

BioMed Central Blog : DIM: hope for ovarian cancer (anti-cancer drug Diindolylmethane (DIM))

"Importantly, Kandala and Srivastava also showed that DIM enhanced the anti-cancer effects of cisplatin in both human ovarian cancer cells and in mice, where a combination of both drugs reduced tumour growth by an extra 50% compared with cisplatin alone. DIM is thus an exciting potential future therapy for ovarian cancer, which could overcome the problems with cisplatin resistance in some women."

in research: Combinations of Resveratrol, Cisplatin and Oxaliplatin Applied to Human Ovarian Cancer Cells

EvidenceUpdates - Interventions for preventing neuropathy caused by cisplatin and related compounds

BACKGROUND:
Cisplatin and several related antineoplastic agents used to treat many types of solid tumors are neurotoxic, and most patients completing a full course of cisplatin chemotherapy develop a clinically detectable sensory neuropathy. Effective neuroprotective therapies have been sought.


AUTHORS' CONCLUSIONS:
At present, the data are insufficient to conclude that any of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxycarbazepine, or Vitamin E) prevent or limit the neurotoxicity of platin drugs among human patients.

Cochrane review: Interventions for preventing neuropathy caused by cisplatin and related compounds

AUTHORS' CONCLUSIONS: At present, the data are insufficient to conclude that any of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxycarbazepine, or Vitamin E) prevent or limit the neurotoxicity of platin drugs among human patients.

Randomized Phase III Clinical Trial Evaluating Weekly Cisplatin for Advanced Epithelial Ovarian Cancer — J. Natl. Cancer Inst.

Thus, increasing dose intensity of cisplatin does not improve PFS or OS compared with standard chemotherapy.

Randomized Phase III Clinical Trial Evaluating Weekly Cisplatin for Advanced Epithelial Ovarian Cancer

"Thus, increasing dose intensity of cisplatin does not improve PFS or OS compared with standard chemotherapy."

science article: Duke continues investigation as geneticist's work retracted (ovarian cancer patients to cisplatin drug therapy)

Phase 1/pharmacology study of intraperitoneal topotecan alone and with cisplatin: potential for consolidation in ovarian cancer.

Adding topotecan to standard treatment for ovarian cancer does not improve progression-free survival

Blogger's Note: discussions/research have been made in the past regarding triple therapies (irrespective of types of therapies) with most resulting, if not all, leading to increased toxicities/no survival advantage

"...Adding topotecan to carboplatin plus paclitaxel, the standard treatment for ovarian cancer, does not improve progression-free survival in patients and leads to greater toxicity, according to a study published online October 11 in the Journal of the National Cancer Institute.

Cisplatin plus paclitaxel, and carboplatin plus paclitaxel, are the most widely accepted first-line regimens for advanced epithelial ovarian cancer. Still, most women relapse and die from their disease. One possible solution is to add a third agent, such as topotecan, which has activity in the treatment of recurrent disease. However, combining topotecan with carboplatin plus paclitaxel as a triplet therapy is problematic because of bone marrow toxicity. So, to integrate topotecan into the standard regimen researchers tested cisplatin plus topotecan followed by carboplatin plus paclitaxel.

The phase III randomized study included 819 women aged 28-78 with newly-diagnosed stage IIB or more advanced ovarian cancer. The study was led by Paul Hoskins, M.D., of the British Columbia Cancer Agency in Vancouver and colleagues from three other groups: the NCIC Clinical Trials Group at Queen's University in Kingston, Canada, the European Organization for Research and Treatment of Cancer – Gynecologic Cancer Group, European Union, and the Grupo Espańol de Investigación en Cáncer de Ovario in Spain.

The women in the study were from Canada and Europe, and were randomly assigned to one of two study groups: the first arm received cisplatin and topotecan, followed by carboplatin and paclitaxel; the second arm received only carboplatin and paclitaxel...."

in research - Abstract: RNAi screening of the kinome identifies modulators of cisplatin response in ovarian cancer cells.

CONCLUSIONS: Our data provides kinase targets that could be exploited to design better therapeutics for ovarian cancer patients. We also demonstrate the effectiveness of high-throughput RNAi screening as a tool for identifying sensitizing targets to known and established chemotherapeutic agents.

Vascular Endothelial Growth Factor Is a Promising ... [Mol Cancer Ther. 2010] - PubMed result

Mol Cancer Ther. 2010 Jul 27. [Epub ahead of print]

Vascular Endothelial Growth Factor Is a Promising Therapeutic Target for the Treatment of Clear Cell Carcinoma of the Ovary.

Mabuchi S, Kawase C, Altomare DA, Morishige K, Hayashi M, Sawada K, Ito K, Terai Y, Nishio Y, Klein-Szanto AJ, Burger RA, Ohmichi M, Testa JR, Kimura T.

Authors' Affiliations: 1Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine; 2Department of Obstetrics and Gynecology, Osaka Police Hospital; 3Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan; 4Women's Cancer Program, 5Cancer Genetics and Signaling Program, and 6Department of Surgery, Fox Chase Cancer Center, Philadelphia, Pennsylvania; and 7Department of Obstetrics and Gynecology, Kansai Rosai Hospital, Amagasaki, Japan.

Abstract

This study examines the role of vascular endothelial growth factor (VEGF) as a therapeutic target in clear cell carcinoma (CCC) of the ovary, which has been regarded as a chemoresistant histologic subtype. Immunohistochemical analysis using tissue microarrays of 98 primary ovarian cancers revealed that VEGF was strongly expressed both in early-stage and advanced-stage CCC of the ovary. In early-stage CCCs, patients who had tumors with high levels of VEGF had significantly shorter survival than those with low levels of VEGF. In vitro experiments revealed that VEGF expression was significantly higher in cisplatin-refractory human CCC cells (RMG1-CR and KOC7C-CR), compared with the respective parental cells (RMG1 and KOC7C) in the presence of cisplatin. In vivo treatment with bevacizumab (Avastin) markedly inhibited the growth of both parental CCC cell-derived (RMG1 and KOC7C) and cisplatin-refractory CCC cell-derived (RMG1-CR and KOC7C-CR) tumors as a result of inhibition of tumor angiogenesis.
The results of the current study indicate that VEGF is frequently expressed and can be a promising therapeutic target in the management of CCC. Bevacizumab may be efficacious not only as a first-line treatment but also as a second-line treatment of recurrent disease in patients previously treated with cisplatin.
Mol Cancer Ther; 9(8); OF1-12. (c)2010 AACR.

Abstract/free access: Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth

Note: in research (cisplatin/radiation resistant cell lines)/highly technical

"This study demonstrates a novel curcumin pre-treatment strategy that could be
implemented in pre-clinical animal models and in future clinical trials for the effective treatment of chemo/radio-resistant ovarian cancers."

Vitamin E neuroprotection for cisplatin neuropathy: A randomized, placebo-controlled trial -- Neurology

Conclusions: This phase III study confirms the neuroprotective role of vitamin E against cisplatin peripheral neurotoxicity. Vitamin E supplementation should be adopted in patients receiving cisplatin-based chemotherapy.

abstract: Administration of cisplatin in three patients with carboplatin hypersensitivity: is skin testing useful?

Alternative intraperitoneal chemotherapy regimens for optimally debulked ovarian cancer

Conclusion: Intraperitoneal chemotherapy regimens using carboplatin or cisplatin and dropping day 8 IP paclitaxel have less toxicity and less discontinuation of therapy