Journal of Experimental & Clinical Cancer Research |- Chemotherapy and skin reactions

Journal of Experimental & Clinical Cancer Research  Chemotherapy and skin reactions

Research

Chemotherapy and skin reactions

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

 Journal of Experimental & Clinical Cancer Research 2012

Published: 28 May 2012

Abstract (provisional)

Background

New chemotherapic agents and new protocols in oncology have led to an increasing survival rate in patients affected by tumors. However, this increased use has been accompanied by a growth in the incidence of cutaneous side effects and a worsening of patients' quality of life. Appropriate management of skin toxicity associated with chemotherapic agents is therefore necessary for suitable drug administration and to improve quality of life and clinical outcomes.

Methods

We have clinically examined 100 patients affected by cancer, determining type, frequency, treatment, and evolution of side effects related to chemotherapy.

Results

The prevalent cutaneous side effects in patients undergoing chemotherapy are skin rash, xerosis, pruritus, paronychia, hair abnormality, and mucositis. The clinical cases are reported in detail.

Conclusion

Oncological therapies have become more selective and have low systemic toxicity because of their high specificity, but cutaneous side effects are common and may worsen the quality of life of these patients.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Earlier detection of bone loss may be in future

Earlier detection of bone loss may be in future

“Right now, pain is usually the first indication that cancer is affecting bones. If we could detect it earlier by an analysis of urine or blood in high-risk patients, it could significantly improve their care,” Fonseca said.

Squamous Cell Carcinoma of the Oral Cavity in Nonsmoking Women: A New and Unusual Complication of Chemotherapy for Recurrent Ovarian Cancer? PLD (pegylated liposomal doxorubicin)

Squamous Cell Carcinoma of the Oral Cavity in Non smokingWomen: A New and Unusual Complication of Chemotherapy for Recurrent Ovarian Cancer?

Abstract
Purpose.
To describe occurrences of oral squamous cell carcinoma (SCC) in patients who had received long-term pegylated liposomal doxorubicin (PLD) for ovarian cancer.

Patients and Methods.
In our cohort of patients on maintenance PLD for ovarian and related mullerian epithelial malignancies, we encountered two patients with invasive SCC of the oral cavity (one of them multifocal) and one with high-grade squamous dysplasia. Review of patients at our institution receiving PLD for recurrent ovarian cancer identified three additional patients. The duration of treatment, cumulative PLD dose, human papillomavirus (HPV) positivity, BRCA status, stage at diagnosis, outcome, and other characteristics are reviewed.

Results.
All five cases were nonsmokers with no known risk factors for HPV and four were negative for p16 expression. Four of the patients had known BRCA mutations whereas one tested negative. Cumulative doses of PLD were >1,600 mg/m(2) given over 30-132 months. Three had SCCs staged as T1N0 oral tongue, alveolar ridge (gingival), and multifocal oral mucosa; one had a T2N0 oral tongue; and one had dysplasia. After excision, two were given radiation but recurred shortly thereafter; the others remain well and have had no further exposure to cytotoxic drugs, including PLD.

Conclusion. 
Awareness of this possible long-term complication during PLD treatment should enhance the likelihood of early detection of oral lesions in these patients. Decisions to continue maintenance PLD after complete response of the original cancer should perhaps consider the benefits of delaying ovarian cancer recurrence versus the possible risk for a secondary cancer. 

The finding of oral SCC in patients on long-term PLD
maintenance should alert oncologists to have a high index of
suspicion with any oral complaints that arise, and suggests a
possible need for regular oral examinations in this treatment
population. How long to continue maintenance with PLD after
a CR has been achieved is an unanswered question. The possible
risks to patients receiving maintenance PLD beyond CR
must be weighed against the presumed benefits of delaying
ovarian cancer recurrence on an individual basis.

Is Renal Thrombotic Angiopathy a Potential Problem in the Chronic Treatment of Ovarian Cancer?

UNC Kidney Center:  thrombotic microangiopathy
                           ~~~~~~~~~~~~~~~~~~

Is Renal Thrombotic Angiopathy a Potential Problem in the Chronic Treatment of Ovarian Cancer?

"Treatments for recurrent ovarian cancer result in clinical
benefit and prolongation of survival times. However, our findings suggest that platinums, PLD (in large cumulative doses), bevacizumab, and possibly gemcitabine may result in cumulative kidney damage. Awareness of these long-term complications should open the way for studies on treatment strategies designed to minimize renal complications."

Abstract

Abstract Background and Objective

Ovarian cancer is usually diagnosed at an advanced stage, with most patients undergoing surgery followed by platinum- and taxane-based chemotherapy. After initial clinical remission, the majority recur, leading to additional treatments, including not only platinums and taxanes but also pegylated liposomal doxorubicin (PLD), gemcitabine, topotecan, and, more recently, bevacizumab, which may extend survival times. PLD, in particular, has been extensively studied by our group, with encouraging therapeutic results. We, however, observed instances of chronic kidney disease (CKD) developing among patients who received long-term treatment for recurrent ovarian cancer. To document the frequency and contributing factors to the emergence of CKD, we initiated a retrospective review at two institutions.

(Kidney damage was defined by pathologic abnormalities
or markers of damage, including abnormalities on blood
and urine tests and radiologic studies.)

Patients and Methods. 

Fifty-six consecutive patients with recurrent ovarian cancer receiving treatment at New York University Cancer Institute were reviewed for the presence of renal disease in 1997–2010. At Shaare Zedek Medical Center, 73 consecutive patients with ovarian cancer were reviewed in 2002–2010. Patients were diagnosed with CKD if they had an estimated GFR <60 mL/minute per 1.73 m² for >3 months and were staged according to the National Kidney Foundation guidelines.

Results. 

Thirteen patients (23%) developed stage ≥3 CKD. Three patients had renal biopsies performed that showed thrombotic microangiopathy. 

Conclusions. 

CKD (chronic kidney disease) is emerging as a potential long-term consequence of current chemotherapy for recurrent ovarian cancer.

• Chronic kidney disease
• Ovarian cancer
• Pegylated liposomal doxorubicin
• Renal thrombotic microangiopathy

paywalled - Gynecologic Oncology - Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer

ScienceDirect.com - Gynecologic Oncology - Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer

Objective

To identify factors that increase the risk of neutropenic events in women with advanced ovarian carcinoma receiving initial chemotherapy.

Methods

Multi-center retrospective study of women with FIGO stage III–IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy from 1995 to 2008. Outcomes were severe (SN; absolute neutrophil count [ANC] < 500/mm³) and febrile neutropenia (FN; ANC < 1000/mm³ and temperature > 38.1 °C). Cumulative risk of neutropenic events was estimated by Kaplan Meier method. Multivariate analysis was by Cox proportional hazard regression.

Results

Three hundred twenty-six patients met inclusion criteria. There were 251 SN events among 140 (43%) patients and 24 FN events among 22 (7%) patients. Univariate predictors of SN were body surface area < 2.0 m² (p = 0.03), body mass index (BMI) < 30 kg/m² (p < 0.01), Caucasian race (p < 0.01), treatment on research protocols (p < 0.01), non-carboplatin-containing regimens (p < 0.01), and planned relative dose intensity (RDI) > 85% of standard (p = 0.02). Women over age 60 were more likely to develop FN (p = 0.05). Multivariate predictors of SN were treatment on research protocols (hazard ratio [HR] 1.93; p < 0.01), Caucasian race (HR 2.13; p = 0.01), and planned RDI > 85% (HR 1.69; p = 0.05); predictors of FN were age > 60 (HR 2.84; p = 0.05) and non-carboplatin containing regimens (HR 4.06; p < 0.01).

Conclusion

While SN is fairly common, FN occurs infrequently in women with EOC undergoing taxane and platin-based chemotherapy and primary prophylactic growth factor support is not indicated. However, women older than 60 years of age receiving non-carboplatin containing regimens are at higher risk for FN and warrant closer surveillance.

Oxaliplatin-related thrombocytopenia

Oxaliplatin-related thrombocytopenia

Oxaliplatin is a third generation platinum compound that inhibits DNA synthesis, mainly through intrastrandal cross-links in DNA. Most of the experience with the clinical use of this drug is derived from colorectal cancer but it is also used in other tumor types such as ovary, breast, liver and non-Hodgkin's lymphoma. Thrombocytopenia is a frequent toxicity seen during oxaliplatin treatment, occurring at any grade in up to 70 % of patients and leading to delays or even discontinuation of the chemotherapy. Although myelossupression is recognized as the main cause of oxaliplatin-related thrombocytopenia, new mechanisms for this side-effect have emerged, including splenic sequestration of platelets related to oxaliplatin-induced liver damage and immune thrombocytopenia. These new pathophysiology pathways have different clinical presentations and evolution and may need specific therapeutic maneuvers. This article attempts to review this topic and provides useful clinical information for the management of oxaliplatin-related thrombocytopenia...........

abstract: A systematic review evaluating the relationship between progression free survival and post progression survival in advanced ovarian cancer

 Blogger's Note:
this is and has been an ongoing issue in clinical trials as most use still use overall survival (OS) (as per this paper and others)  as the endpoint as opposed to progression free survival; it is a technical debate having wide implications for ovarian cancer treatments/patients, without access to the full text paper and based on the abstract alone,  one outstanding issue would be the impact of QOL/side effects/number of prior treatments, so in plain english as an example - clinical trial x includes standard treatment vs other, no more than eg. 3 prior chemos would be a component of the clinical trial - therefore - what was/is the mix of patients in the trial - all of which impact survival ratios irrespective of PFS/OS; opinions as usual are welcome
                                      ~~~~~~~~~~~~~~~~~

A systematic review evaluating the relationship between progression free survival and post progression survival in advanced ovarian cancer:




Objective 
Although overall survival is the ultimate goal of cancer therapy, many clinical and health economic decisions are taken when only progression free survival (PFS) data are available. This study evaluates the relationship between PFS and post progression survival (i.e. the time between disease progression and death) to estimate how many months a new drug for ovarian cancer might add to overall survival if the number of months the drug added to PFS (relative to a standard drug) was already known.

Methods 
A literature search was conducted over Medline for randomised controlled trials published between January 1990 and July 2010 that evaluated the effect of a drug treatment in comparison to alternative drug treatment in patients with either advanced stage primary or recurrent ovarian cancer.
A systematic review of progression free and post progression survival (PPS) was performed. The relationship between PFS and PPS was evaluated by a graphical method and standard statistical tests.

Results
Thirty-seven trials involving 15,850 patients met the inclusion criteria. The review found that increases in median PFS generally lead to little change in post-progression survival. Percentage gains in PFS are generally associated with no percentage gains or with very slight percentage gains or losses in post-progression survival

Conclusion
If the effect of a new drug treatment for ovarian cancer is to extend median PFS by x months, then it is reasonable to estimate that the treatment will also extend median overall survival by x months. This information will be useful for individual and collective decision making.

open access: Impaired Cognitive Function and Hippocampal Neurogenesis following Cancer Chemotherapy (Chemobrain)

 Blogger's Note: also refer to previous post regarding chemobrain research in mice, differences in the 2 studies include chemotherapy agents, but, same bottom line results (confirmation of side effects/adverse effects of chemotherapy treatments)

Impaired Cognitive Function and Hippocampal Neurogenesis following Cancer Chemotherapy


Conclusions (abstract): 
Our results show that chronic treatment with either of two commonly used chemotherapeutic agents impairs cognitive ability and suggest that strategies to prevent or repair disrupted hippocampal neurogenesis may be effective in ameliorating this serious side effect in cancer survivors.

open access: The Effects of Chemotherapy on Cognitive Function in a Mouse Model: A Prospective Study (Chemobrain)

Blogger's Note:  note article for observations regarding duration of chemobrain/MRI imaging

The Effects of Chemotherapy on Cognitive Function in a Mouse Model: A Prospective Study

science news: Menopause clinicians support new advice on steroid use (Corticosteroids/glucocorticoids)

Menopause clinicians support new advice on steroid use

 (Corticosteroids/glucocorticoids)


.............Dr Tobie de Villiers, President of the International Menopause Society (IMS), commented, "Bone loss is a concern for all women around the age of menopause, and especially for the almost 5% of postmenopausal women worldwide who take oral glucocorticoid therapy. The IMS encourages women to be aware of this potentially dangerous side-effect of therapy and to discuss what precautions can be taken with their doctors."
Continuing, Dr de Villiers said "The ovaries stop producing estrogen around the time of the menopause, meaning that women find that the risk of bone loss and osteoporosis increases. This is already difficult for many women to cope with, so we need to be especially careful that the medicines which women take for other conditions don't actually harm women's bones. Glucocorticoids are important and valuable medicines, but like all medicines they have side effects and their use must be customised and monitored. Women, especially women after their menopause, need to be more aware of the possibility of this serious side-effect. These guidelines are aimed at allowing national organisations to develop effectively."

AACR: Selumetinib Controlled Recurrent Low-grade Serous Ovarian Cancer

Selumetinib Controlled Recurrent Low-grade Serous Ovarian Cancer:

• Selumetinib controlled the disease in 81 percent of patients.
• Median progression-free survival was 11 months.
• Patients experienced minimal side effects.

CHICAGO — Selumetinib, a small-molecule MEK inhibitor, demonstrated the ability to control low-grade serous ovarian or peritoneal cancer, according to phase II study results presented at the AACR Annual Meeting 2012, held here March 31 – April 4.
The first line of defense against low-grade serous ovarian cancer is surgery, followed by cytotoxic chemotherapy. However, this is a slow-growing cancer and does not respond well to traditional chemotherapies, which target fast-growing cells.
Seeking a more rational treatment approach, Gynecologic Oncology Group (GOG) researchers led by John Farley, M.D., a professor at Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center in Omaha, Neb., used selumetinib to target the MEK-1/2 protein kinase in the MAPK pathway, which is known to mutate in this form of cancer.
GOG researchers assigned 52 women to 100-mg doses of selumetinib orally twice daily in four-week cycles; 33 percent underwent 12 or more cycles. Prior to the study, 58 percent of patients had received three or more rounds of chemotherapy.
Selumetinib controlled the disease in 81 percent of patients. Specifically, eight patients had complete or partial responses to treatment, and 34 had stable disease. The median survival rate without cancer progression was 11 months, and 63 percent of patients had progression-free survival longer than six months. In addition, selumetinib was well tolerated, with three patients experiencing grade 4 adverse events.
“The results were striking,” said Farley. “Many of the patients in the study had received multiple rounds of chemotherapy and were running out of options. By using these tumors’ historical inherent molecular aberrations to select patients for a treatment that in theory could exploit these abnormalities, we took an important step toward individualized cancer therapies.”
In addition to studying the impact of selumetinib on this type of ovarian cancer, investigators were also interested in how patients with RAS/RAF mutations responded to the drug. The team analyzed the tumor DNA from 34 patients, 62 percent of whom had some form of RAS/RAF mutation. Ultimately, they found that RAS/RAF mutations had no impact on patient response.
The study was funded by the National Cancer Institute.

Commentary: Aromatase inhibitors and musculoskeletal adverse events : The Lancet Oncology

Aromatase inhibitors and musculoskeletal adverse events : The Lancet Oncology

".........Because symptom collection is so variable between trials, researchers could look for correlations between changes in patient-reported quality of life and breast-cancer outcomes. Nevertheless, if clinical research confirms a link between emergent symptoms or changes in quality of life and breast-cancer outcomes, further pharmacogenomic and pharmacogenetic studies could help to elucidate the mechanisms. Although confirmation of the association between emergent symptoms with aromatase inhibitors and risk of breast-cancer recurrence would help to guide clinical advice, based on current evidence clinicians should not use the onset of musculoskeletal symptoms to infer which patient will, or will not, benefit from adjuvant treatment with aromatase inhibitors."

abstract: Does long-term treatment with Doxil(®) predispose patients to oral cancer?

Does long-term treatment with Doxil(®) predispose patients to oral cancer?

Abstract

We present a possible adverse reaction related to long-term use of Doxil(®) in female patients. We believe that long-term use of Doxil(®) may predispose female patients to oral squamous cell carcinoma. The patients in this report were not exposed to the common risk factors related to oral cancer formation such as smoking or alcohol consumption.  

Both patients were 59-year-old females.

The first patient was diagnosed in 2001 with stage IIIC ovarian cancer. Seven years following treatment with Doxil(®), she was diagnosed with stage III squamous cell carcinoma of the right maxilla.

The second patient was diagnosed with Kaposi's sarcoma with evidence of spread to the lungs. Four years following treatment with Doxil(®) she was diagnosed with stage I squamous cell carcinoma of the left maxilla.

A literature review did not reveal any report on Doxil(®) and predisposition to oral cancer; however, we found an abstract that was presented at the last annual meeting of the American Society of Clinical Oncology (ASCO) by Cannon et al.

When we combine the data from Cannon et al. and the data presented here, a total of six female patients developed an epithelial carcinoma of the oral cavity following long-term treatment with Doxil(®).

We believe that a large-scale study should be initiated on patients that were treated with Doxil(®) for more than 3 years, since these patients might be at risk for developing secondary cancer of the oral cavity.

abstract: Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer

Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer.


Abstract

OBJECTIVE: 
To identify factors that increase the risk of neutropenic events in women with advanced ovarian carcinoma receiving initial chemotherapy.

METHODS: 
Multi-center retrospective study of women with FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy 1995-2008.......

CONCLUSION:
While SN is fairly common, FN occurs infrequently in women with EOC undergoing taxane and platin-based chemotherapy and primary prophylactic growth factor support is not indicated. However, women older than 60 years of age receiving non-carboplatin containing regimens are at higher risk for FN and warrant closer surveillance.

abstract: Antiangiogenic Agents in Combination With Chemotherapy for the Treatment of Epithelial Ovarian Cancer

Objective: The purpose of this review was to provide an overview of angiogenesis, including the rationale for targeting angiogenesis as a treatment strategy for epithelial ovarian cancer (EOC) and to discuss available clinical trial data with antiangiogenic agents in EOC, with a focus on combinations with chemotherapy.

Methods: This was a literature review of clinical studies evaluating select antiangiogenic agents in combination with traditional cytotoxic chemotherapy for the treatment of EOC.

Results: Several therapies that target angiogenesis-specific pathways are undergoing clinical development for EOC. Although some of these agents have demonstrated single-agent activity for EOC, there is considerable interest in combining this treatment strategy with chemotherapy in an effort to potentially improve treatment benefits in this patient population. Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, is the most studied antiangiogenic agent in EOC and has shown efficacy as monotherapy and combined with chemotherapy in both the relapsed/recurrent and first-line settings. However, results from recent phase 3 trials raise questions regarding patient selection and optimal dose, schedule, and duration of bevacizumab therapy. Other agents in various phases of testing include aflibercept (VEGF Trap), a fusion protein that binds all isoforms of VEGF; multitargeted antiangiogenic tyrosine kinase inhibitors (eg, BIBF 1120, cediranib, pazopanib, sorafenib); and AMG 386, a selective angiopoietin inhibitor. Toxicities associated with VEGF inhibition are also a concern with antiangiogenic therapy, including hypertension, proteinuria, thromboses, and gastrointestinal perforation.

Conclusions: Results from recently completed and ongoing clinical trials combining antiangiogenic agents with chemotherapy are awaited in hopes of expanding therapeutic options for patients with EOC.

press release: Mass. General researchers find novel way to prevent drug-induced liver injury

abstract: Whole-brain radiation therapy of brain metastasis.

Prog Neurol Surg. 2012;25:82-95. Epub 2012 Jan 6.

Source

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Princess Margaret Hospital, University of Toronto, Toronto, Ont., Canada.

Abstract

The purpose of this report was to review the role of whole brain radiotherapy (WBRT) in the management of brain metastases. In particular, we review the role of WBRT as a prophylactic therapy, and the role of surgery and stereotactic radiosurgery (SRS) with respect to WBRT, by discussing the relevant randomized controlled trials. WBRT is associated with toxicities and this may influence the decision to use WBRT and, therefore, we review both the acute side effects of WBRT and the moreserious late side effects of neurocognitive impairment and leukoencephalopathy. As patients are living longer with brain metastases the role of WBRT is moving forward; however, using modern radiation technology we may be able to reduce the morbidity of this therapy. We present an extreme case of re-re-treatment WBRT with hippocampal sparing and simultaneous integrated boosts to multiple lesions as one of the future directions under evaluation.

Warfarin (Coumadin)- fp notebook update

Zoledronic acid preserves bone mineral density in premenopausal women who develop ovarian failure due to adjuvant chemotherapy: Final results from CAL

Note: side effects

INTERPRETATION: ZA every 3 months is well tolerated and prevents rapid bone loss in premenopausal women that develop CIOF. Giving ZA with rather than 1 year after the start of adjuvant chemotherapy is the preferred sequence to prevent bone loss.

abstract: Aromatase inhibitor therapy: toxicities and management strategies in the treatment of postmenopausal women with hormone-sensitive early brea