In the Journals

Single adjuvant chemotherapy course safe, effective for high-risk testicular cancer

A single course of adjuvant bleomycin, etoposide and cisplatin chemotherapy appeared safe and effective among a cohort of men with high-risk primary testicular cancer, according to results of the phase 3, single-arm, prospective 111 study published in European Urology.

“Men with stage I nonseminoma germ cell tumors of the testis have an excellent prognosis, but a subgroup with lymphovascular invasion in the primary site have a high risk for recurrence that requires intensive chemotherapy as salvage therapy, and about one-third have subsequent major surgery,” Robert Huddart, MBBS, MRCP, FRCR, PhD, professor in the department of urological cancer at The Institute of Cancer Research in the U.K., told Healio.

“Many of these men are offered adjuvant chemotherapy to reduce relapse risk," he added. "Over the years, it was realized that for patients who relapse, three cycles of higher-dose bleomycin, etoposide and cisplatin [BEP] was sufficient, so four cycles became a less attractive option. This raised the question as to whether one cycle was enough for relapse prevention.”

To answer that question, Huddart and colleagues assessed whether one cycle of adjuvant BEP chemotherapy conferred rates of recurrence comparable to two cycles of the combination therapy among 246 men (median age, 31 years; interquartile range [IQR], 25-39) with vascular invasion-positive stage I nonseminoma germ cell tumors of the testis or combined seminoma plus nonseminoma germ cell tumors of the testis.

Men received one cycle of 30,000 IU bleomycin on days 1, 8 and 15, 165 mg/m² etoposide on days 1 to 3, and 50 mg/m² cisplatin on days 1 and 2, plus antibacterial and granulocyte colony-stimulating factor prophylaxis. All men received regular imaging and tumor marker assessment for 5 years. Researchers excluded 10 men due to increasing tumor markers at baseline.

Two-year malignant recurrence served as the primary endpoint.

Median follow-up was 49 months (IQR, 37-60).

Four men experienced malignant recurrence, at 6, 7, 13 and 27 months. All underwent treatment with second-line chemotherapy and surgery, and three remained recurrence-free at 5 years.

At 2 years, results showed a malignant recurrence rate of 1.3% (95% CI, 0.3-3.7), nearly identical to the rate in prior studies of two BEP chemotherapy cycles, according to researchers. Three men developed nonmalignant recurrences with localized teratoma differentiated, rendered disease-free after surgery.

Researchers observed one or more serious adverse events among 41% of men during treatment. These included grade 3 to grade 4 neutropenia (32%), leukopenia (17%), febrile neutropenia (6.8%), thrombocytopenia (3.4%) and damage to hearing (2.6%).

“Our study met its primary endpoint to show that less than 5% of patients relapse after adjuvant chemotherapy, rather than the expected 50%, with some but not excessive toxicity,” Huddart told Healio. “This confirms previous research that this is an effective way to manage this patient group that would be predicted to reduce total chemotherapy to the population; thus, it is a cheaper and safe approach. Most research being conducted now is on better markers so adjuvant therapy can be focused on patients with highest relapse risk.”

These findings add to the growing body of evidence on the efficacy of single-dose adjuvant BEP for men with high-risk, stage I nonseminomatous germ cell tumor of the testis, Torgrim Tandstad, MD, PhD, consultant in medical and radiation oncology at The Cancer Clinic at St. Olavs University Hospital in Norway, wrote in an accompanying editorial.

“To date, three large prospective studies have demonstrated the efficacy of this nonsurgical approach in clinical stage I nonseminomatous germ cell tumor of the testis,” Tandstad wrote. “Together, these prospective studies included 937 patients treated with one cycle of adjuvant bleomycin, etoposide and cisplatin, with more than 60% of the patients having high-risk disease.” – by Jennifer Southall

For more information:

Robert Huddart, MBBS, MRCP, FRCR, PhD, can be reached at The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP; email: robert.huddart@icr.ac.uk.

Disclosures: The study was funded by Cancer Research U.K. and Queen Elizabeth Hospital Birmingham Charity. Huddart reports nonfinancial support from Janssen and Roche; grants from Cancer Research U.K. and Merck Sharp & Dohme outside of the submitted work; and personal fees from Bristol-Myers Squibb, Merck Sharp & Dohme and Roche. Please see the study for all other authors’ relevant financial disclosures. Tandstad reports no relevant financial disclosures.

A single course of adjuvant bleomycin, etoposide and cisplatin chemotherapy appeared safe and effective among a cohort of men with high-risk primary testicular cancer, according to results of the phase 3, single-arm, prospective 111 study published in European Urology.

“Men with stage I nonseminoma germ cell tumors of the testis have an excellent prognosis, but a subgroup with lymphovascular invasion in the primary site have a high risk for recurrence that requires intensive chemotherapy as salvage therapy, and about one-third have subsequent major surgery,” Robert Huddart, MBBS, MRCP, FRCR, PhD, professor in the department of urological cancer at The Institute of Cancer Research in the U.K., told Healio.

“Many of these men are offered adjuvant chemotherapy to reduce relapse risk," he added. "Over the years, it was realized that for patients who relapse, three cycles of higher-dose bleomycin, etoposide and cisplatin [BEP] was sufficient, so four cycles became a less attractive option. This raised the question as to whether one cycle was enough for relapse prevention.”

To answer that question, Huddart and colleagues assessed whether one cycle of adjuvant BEP chemotherapy conferred rates of recurrence comparable to two cycles of the combination therapy among 246 men (median age, 31 years; interquartile range [IQR], 25-39) with vascular invasion-positive stage I nonseminoma germ cell tumors of the testis or combined seminoma plus nonseminoma germ cell tumors of the testis.

Men received one cycle of 30,000 IU bleomycin on days 1, 8 and 15, 165 mg/m² etoposide on days 1 to 3, and 50 mg/m² cisplatin on days 1 and 2, plus antibacterial and granulocyte colony-stimulating factor prophylaxis. All men received regular imaging and tumor marker assessment for 5 years. Researchers excluded 10 men due to increasing tumor markers at baseline.

Two-year malignant recurrence served as the primary endpoint.

Median follow-up was 49 months (IQR, 37-60).

Four men experienced malignant recurrence, at 6, 7, 13 and 27 months. All underwent treatment with second-line chemotherapy and surgery, and three remained recurrence-free at 5 years.

At 2 years, results showed a malignant recurrence rate of 1.3% (95% CI, 0.3-3.7), nearly identical to the rate in prior studies of two BEP chemotherapy cycles, according to researchers. Three men developed nonmalignant recurrences with localized teratoma differentiated, rendered disease-free after surgery.

Researchers observed one or more serious adverse events among 41% of men during treatment. These included grade 3 to grade 4 neutropenia (32%), leukopenia (17%), febrile neutropenia (6.8%), thrombocytopenia (3.4%) and damage to hearing (2.6%).

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“Our study met its primary endpoint to show that less than 5% of patients relapse after adjuvant chemotherapy, rather than the expected 50%, with some but not excessive toxicity,” Huddart told Healio. “This confirms previous research that this is an effective way to manage this patient group that would be predicted to reduce total chemotherapy to the population; thus, it is a cheaper and safe approach. Most research being conducted now is on better markers so adjuvant therapy can be focused on patients with highest relapse risk.”

These findings add to the growing body of evidence on the efficacy of single-dose adjuvant BEP for men with high-risk, stage I nonseminomatous germ cell tumor of the testis, Torgrim Tandstad, MD, PhD, consultant in medical and radiation oncology at The Cancer Clinic at St. Olavs University Hospital in Norway, wrote in an accompanying editorial.

“To date, three large prospective studies have demonstrated the efficacy of this nonsurgical approach in clinical stage I nonseminomatous germ cell tumor of the testis,” Tandstad wrote. “Together, these prospective studies included 937 patients treated with one cycle of adjuvant bleomycin, etoposide and cisplatin, with more than 60% of the patients having high-risk disease.” – by Jennifer Southall

For more information:

Robert Huddart, MBBS, MRCP, FRCR, PhD, can be reached at The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP; email: robert.huddart@icr.ac.uk.

Disclosures: The study was funded by Cancer Research U.K. and Queen Elizabeth Hospital Birmingham Charity. Huddart reports nonfinancial support from Janssen and Roche; grants from Cancer Research U.K. and Merck Sharp & Dohme outside of the submitted work; and personal fees from Bristol-Myers Squibb, Merck Sharp & Dohme and Roche. Please see the study for all other authors’ relevant financial disclosures. Tandstad reports no relevant financial disclosures.