Perspectives on Ovarian Cancer: Treatment, Interventions, and Psychosocial Concerns

At a symposium held in conjunction with the Twenty-Seventh Annual Congress of the Oncology Nursing Society, three leaders in gynecologic oncology and supportive care presented current data on treatment, symptom management, and psychosocial needs in women with ovarian cancer. Topics included the newest chemotherapy combinations, prevention and management of major chemotherapy side effects, and patient perspectives on the need for psychosocial support.

This program was supportedby an educational grant fromOrtho Biotech Products, L.P.

Speakers

Chemotherapeutic Management in Ovarian Cancer: Initial and Relapsed  

Since the 1970s, the 5-year survival rates of persons with ovarian cancer have increased dramatically. “Women with ovarian cancer are now living longer, making improvements in quality of life care as well in treatment of disease especially important,” said Alan N. Gordon, MD, Director, Research in Gynecologic Oncology, Texas Oncology, Dallas. In the hope of improving overall outcomes for women with ovarian cancer, researchers continue to study new chemotherapy agents and combinations, aimed at both increasing efficacy and reducing toxicity.

Chemotherapy for Newly Diagnosed Disease
The standard chemotherapeutic approach to the initial treatment of ovarian cancer consists of a platinum/taxane combination (Table 1). In developing recent chemotherapy strategies, issues have included integration of taxane therapy, selection of platinum compound, and determination of taxane optimal dose and schedule.

Adding a taxane
In comparing cisplatin/cyclophosphamide with cisplatin/paclitaxel, McGuire and Piccart study groups showed significant improvements in progression-free survival and overall survival rates with the paclitaxel arm. “These and other data led to the integration of taxane agents into front-line treatment for ovarian cancer,” said Dr. Gordon.

Choosing a platinum compound
Cisplatin is associated with major side effects, such as nausea and vomiting and electrolyte disturbance. Carboplatin is less nephrotoxic and easier to administer, but is associated with greater hematologic toxicity. Ozols and colleagues (1999) and du Bois and colleagues (1999) treated women with ovarian cancer with either cisplatin/paclitaxel or carboplatin/paclitaxel regimens. In both studies, the progression-free survival times were similar in the two treatment arms. However, largely due to the toxicity data, the carboplatin/taxane combination became a standard therapy for the initial treatment of advanced ovarian cancer, Dr. Gordon noted.

Choosing taxane dosage
Paclitaxel is associated with a different side effect profile, depending on the dose, method of infusion, and duration of infusion; however, there appears to be no evidence for dose response or schedule dependency for currently standard regimens. In terms of infusion times, no link between longer exposure and improved response has been noted, but clinically, shorter infusion is associated with greater degree of neurotoxicity, longer infusion with greater degree of hematologic toxicity. Vassey and colleagues (2001) recently randomized women with ovarian cancer (all stages) to receive either carboplatin/docetaxel or carboplatin/paclitaxel. Efficacy results were similar, but significant differences emerged in toxicity. With paclitaxel, grade 2/3 neuropathy was significantly higher. With docetaxel, grade 4 neutropenia was significantly higher. In addition, paclitaxel was associated with significantly greater physician-scored neurotoxicity, even after completion of therapy.

“For patients with thrombocytopenia or neurotoxicity, reducing drug doses or switching to an alternative drug may be warranted [Table 1]. For those who cannot tolerate concurrent combination therapy, sequential combination therapy may be a consideration,” Dr Gordon noted.

Chemotherapy for Recurrent Disease
In persons with ovarian cancer, recurrence is common. “In treating patients with a recurrence of ovarian cancer, it is important not only to target the disease, but also to assure reduced toxicity, increased convenience, and optimal quality of life,” said Dr. Gordon. Many agents are currently used as second-line therapy for ovarian cancer; however, most show similar response rate (30% to 40%) and progression-free survival (3 to 4 months) outcomes. In one phase III study, Gordon and colleagues (2001) compared pegylated liposomal doxorubicin (PLD) with topotecan for the treatment of recurrent ovarian cancer. Overall response rates (20% PLD vs 17% topotecan) and time to progression (18 weeks each arm) were similar in the two arms; however, in platinum-sensitive patients, PLD had superior progression-free (28.9 vs 23.3 weeks) and overall survival (108 vs 71.1 weeks). Topotecan had significant rates of neutropenia, thrombocytopenia, and leukopenia, while PLD was associated with significant palmar-plantar erythrodysesthesia (PPE) and stomatitis. “However, it has now been identified that PPE and stomatitis can be decreased, by reducing the dose of PLD from 50 mg/m2 every 4 weeks to 40 mg/m2 every 4 weeks,” Dr. Gordon said (Rose et al 2001; Campos et al 2001). In summary, the Gordon study showed comparable efficacy with the two treatment arms (PLD superior in platinum-sensitive patients), but a more convenient dosing schedule (1 hour infusion vs infusion every day for 5 days) and reduced toxicity with PLD, showing less myelosuppression, thromobocytopenia, and alopecia. Because of these and other data, future directions in chemotherapy development for the treatment of ovarian cancer may focus on liposome technology and other methods to reduce toxicity and target the tumor.

In closing, Dr. Gordon indicated that several areas of research appear hopeful for future improvement in the chemo-therapeutic management of ovarian cancer. “Defining the role of adjuvant and neoadjuvant surgery, and using triple-agent combination therapies, sequential doublet and alternating doublet regimens, and biologic therapies may hold promise for prolonged remissions and improved survival in persons with ovarian cancer,” the speaker concluded.

Focus on Physical Concerns and Side Effect Management

“While ovarian cancer is a persistent disease, often presenting with repeated remissions and relapses, patients with ovarian cancer are even more persistent,” said Lois Almadrones, RN, MS, CFNP, MPA, Program Chair, Clinical Nurse Specialist, Gynecology Service, Memorial Sloan-Kettering Cancer Center, New York, New York. In helping survivors of ovarian cancer to live with this disease, it is imperative that oncology nurses provide education regarding which chemotherapy side effects to expect—palmar-plantar erythrodyses-thesia (PPE), peripheral neuropathy, hypersensitivity reactions—and how to manage them optimally. In addition, intraperitoneal therapy and minimally invasive surgery may play an important role in the care of patients with ovarian cancer.

Palmar-Plantar Erythrodysesthesia
PPE, also called hand-foot syndrome, is thought to be dose- and cycle-dependent and has typically been associated with agents such as liposomal doxorubicin, 5-fluorouracil, capecitabine, and (less commonly) doxorubicin. PPE is characterized by skin erythema at the pressure points, including the hands, feet, belt and bra lines, and in rare cases vulva-vaginal area. Erythema may be accompanied by pain, tingling, burning, and skin desquamation. Often, PPE can be prevented or minimized through patient education in monitoring pressure-sensitive areas for early signs and symptoms. In addition, patients should avoid tight clothes and shoes, vigorous pressure or friction to the skin, rigorous activity, excess heat (hot water), and sunlight for 3 days after treatment. “Patients need to report any symptoms of PPE immediately to their nurse or physician,” Ms. Almadrones advised. In the case of liposomal doxorubicin, many clinicians report success in avoiding PPE by delaying therapy by 1 week and/or reducing the dose from 50 to 40 mg/m2 every 4 weeks. Some nonpharmacologic interventions for PPE include use of cool water soaks, ice packs, and cooling creams. Pharmacologically, vitamin B6 (pyridoxine) and dexamethasone have been used but have not been tested in controlled clinical trials.

Peripheral Neuropathy
Peripheral neuropathy occurs commonly with cisplatin, paclitaxel, and carboplatin. This side effect is characterized by injury, inflammation, or degeneration of the peripheral nerve fibers, potentially affecting sensory (touch, pain, temperature, position, vibratory sense), motor (voluntary movement, muscle tone, coordination), and autonomic functions (involuntary movement). “Oncology nurses should carefully assess patients for this symptom prior to treatment and upon routine follow-ups. Pre-existing neuropathy may indicatethe need for an alteration in therapy to avoid synergistic toxicity,” said Ms. Almadrones. Protective agents, such as amifostine and glutamine, may be used to prevent or minimize neuropathy in patients undergoing chemotherapy. Vahdat and colleagues (2001) recently found that use of glutamine (10 g tid X 4 days), given 24 hours after high-dose paclitaxel treatment, was associated with significantly reduced peripheral neuropathy, motor weakness, deterioration of gait, and interference with daily activities compared with placebo.

Management of peripheral neuropathy may include the use of topical analgesics (eg, lidocaine patch 5%, capsaicin cream) or pharmacologic agents such as tricyclic antidepressants or anticonvulsants.

Hypersensitivity Reactions
The main agents causing hypersensitivity reactions in patients with ovarian cancer include carboplatin, paclitaxel, docetaxel, cisplatin and bleomycin (germ cell disease), with carboplatin being the number one culprit. In assessing hyperreactivity reactions, it is important for oncology nurses to note the differences between carboplatin and paclitaxel. Hypersensitivity reactions to paclitaxel generally occur within the first few minutes of the first or second course of therapy. Symptoms include chest tightness, shortness of breath, angiodema, back pain, urticaria, and blood pressure changes. In contrast, reactions to carboplatin occur after multiple doses, typically 2 to 4 days after the eighth treatment (Markman et al 1999). Symptoms include skin toxicity (rash), chest tightness, blood pressure changes, and facial swelling. “Patients need to be instructed to report any hypersensitivity symptoms immediately, and should especially be aware of the symptoms of carboplatin hypersensitivity as these may develop in the home environment,” Ms. Almadrones noted. Treatment is immediately discontinued and, in the case of paclitaxel, may be restarted slowly. For those with reactions to carboplatin, alternative treatment regimens must be considered. “Interestingly, new methods to predict hypersensitivity to carboplatin are currently under study,” Ms. Almadrones said. In one study, Zanotti and colleagues (2001) used intradermal injection of 0.02 mL undiluted aliquot, and found that reaction to this preparation showed a 99% predictive value for reaction to carboplatin.

Intraperitoneal Therapyand Minimally Invasive Surgery
According to Ms. Almadrones, ovarian cancer is unique in that it stays in the intraperitoneal cavity throughout the extent of the disease. Thus, intraperitoneal therapy (usually with cisplatin) represents an effective treatment option for some patients. Patients who have small-volume ovarian cancer, good peritoneal cavity distribution, and peripheral neuropathy < grade 1 (if cisplatin is used) are good candidates. The side effects of this procedure include abdominal bloating for 48 hours, increased urination for 48 hours, catheter malfunction or infection, abdominal pain, chemical peritonitis (rare), bowel or bladder perforation (rare), and drug-related effects. Thus, patients should be asked to wear loose-fitting clothes for 48 hours, and to call their nurse or physician immediately if they experience severe abdominal pain, fever > 101° F, port site erythema, purulent drainage, or watery diarrhea (sign of perforation).

Finally, minimally invasive surgery may be beneficial in some persons with ovarian cancer. This approach may be used to assess disease status after initial therapy, and to assess the peritoneal cavity for potential intraperitoneal therapy and port placement. Advantages include discharge the same day as surgery, decreased postoperative pain, cosmetic superiority, and rapid recovery time. However, Ms. Almadrones cautioned, this procedure is costly and requires a highly skilled and experienced surgeon..”

In closing, Ms. Almadrones noted that “oncology nurses play a key role in optimizing the care and quality of life of patients with ovarian cancer by informing them about what to expect, what to report, and how to manage in terms of treatment side effects.”

Living with Ovarian Cancer: Women’s Perspectives on Psychosocial Concerns

“To offer optimal care to women who are living with ovarian cancer, we as oncology nurses need to ensure a comprehensive assessment that includes psychosocial issues. In doing so, our focus should be not only on the broad range of issues that may arise with this disease, but also on the needs and wishes of each individual patient throughout the peridiagnosis, diagnosis, treatment, and post-treatment intervals,” said Margaret I. Fitch, RN, PhD, Head, Oncology Nursing and Supportive Care, Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario. Dr. Fitch presented an overview of the perspectives of women living with ovarian cancer, as collected through in-depth interviews, national surveys, and focus group sessions.

Peridiagnostic and Diagnostic Intervals
According to Dr. Fitch, before being diagnosed with ovarian cancer, women reported feeling frustrated with the inability to obtain a definitive diagnosis. Not only were they confused about their symptoms, but their family physicians seemed equally perplexed. They reported not having realized that their symptoms were those of cancer, but rather questioning whether they were related to menopause, aging, or irritable bowel syndrome. After seeing specialist after specialist, the women felt that they were neither heard nor believed. By the time of diagnosis, the women felt drained and emotionally vulnerable.

Upon hearing the diagnosis—ovarian cancer—the women reported being shocked, overwhelmed, and forever changed. While the peridiagnostic period seemed to move too slowly, once the diagnosis was made, everything began to race. “Women reported having to make arrangements for hospitalization, children, and household tasks, often without time for a second opinion. Indeed, the women reported having little input in initial treatment decisions, as they were too ill and felt too hurried,” Dr. Fitch explained.

Treatment Interval
“The treatment phase of life with ovarian cancer was most often characterized as ‘just needing to get focused and get through the therapy’,” Dr. Fitch noted. The most frequent problems reported by older women undergoing treatment were side effects, bowel difficulties, fear of recurrence, difficulty sleeping, fear of dying, and household responsibilities (range 23% to 54%). In contrast, younger women reported more problems, more often. They included side effects, fear of recurrence, difficulty sleeping, fear of dying, difficulty concentrating, anger, body image, bowel difficulty, sex issues, and menopause (range 44% to 64%) (Fitch et al 2000). Importantly, in no case did 100% of women feel they received adequate help for a given problem (received adequate help range: 17% sexual function to 85% pain). In addition, a significant number of women reported being dissatisfied with the amount of information they received on physical and psychosocial issues (range 11% to 44% dissatisfied). In women with no recurrence, 55% reported wanting to talk about their difficulties, and 10% had trouble communicating with healthcare professionals. In those with recurrence, 77% wanted to talk about these issues, and 15% experienced difficulty discussing them with their healthcare providers (Fitch et al 2000). “These findings pose a challenge to oncology professionals to implement innovative ways of communicating and of assessing and addressing both the physical and psychosocial needs of patients during the treatment interval,” Dr. Fitch said.

Post-Treatment Interval
Once initial treatment was finished, women reported having time to reflect on the disease, treatment, and the process of trying to restore their roles in their family and workplace. As part of this period, the women sought to re-identify what was to be prioritized in their lives. The greatest difficulty was in learning to live with the fear of recurrence, with the “time bomb” of ovarian cancer. However, many women described being enriched by the illness experience, as having closer relationships and a greater appreciation of life. Despite this, women who experienced disease recurrences still experienced shock and devastation at the news and the need to undergo treatment yet again. Women with recurrence also expressed concern that healthcare professionals had disengaged or given up on them, just when the women needed their care the most.

In conclusion, Dr. Fitch urged all oncology nurses to discuss both the physical and psychosocial issues of ovarian cancer with their patients, and to utilize referrals and a multidisciplinary collaborative approach to provide optimal care in meeting the needs of women with this debilitating disease.

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