CANCER GUIDE CONSULTATIONS - CASE HISTORIES Rosemary Caruso Rosemary Caruso, 42, an award-winning playwright who was married with one child, an 6-year old daughter, was diagnosed in early 1994 with Stage II epithelial ovarian cancer. At Columbia-Presbyterian Hospital in New York, she underwent a complete hysterectomy with removal of ovaries, followed by chemotherapy, the first-line standard combination of cyclophosphamide and cisplatin. After six rounds of treatment, she had second-look surgery that showed no spread of cancer, and her CA-125 tumor marker was in the normal range. Her gynecologic oncologist at Columbia-Presbyterian felt that she was in remission and her treatment was completed. The prognosis for Stage II ovarian cancer under these circumstances is reasonably good. However, approximately one year later Rosemary was suffering lower abdominal pain and went to her oncologist. Her CA-125 was over 700, and a physical exam followed by a CAT scan revealed a large soft-ball sized tumor in her pelvis at the site of prior surgery. Her oncologist did not believe that the recurrent tumor was readily operable and recommended chemotherapy to reduce its size in the hopes of performing surgery. A combination of taxol and cisplatin was tried with no success, followed by a round of vinorelbine, followed by adriamycin. Her tumor remained stable for a period of time with these regimens but ultimately, after nine months of chemotherapy, the pelvic tumor progressed to the size of cantaloupe and a CAT scan revealed several small metastatic masses in both lungs. At this point, Rosemary was informed by her oncologist that her tumor was inoperable. Such a procedure would be highly complex, requiring extensive plastic surgery which might not succeed in properly closing the wound to prevent infections. Further, he said that additional chemotherapy, which he would be willing to try, was not likely to succeed. He informed her that she had about six months to live. Rosemary went for a second opinion to a leading gynecologic oncologist at Memorial Sloan-Kettering in New York City, and she was offered chemotherapy but also told that she likely had 3-6 months to live. At this point, in late 1995, Rosemary was searching for any possible leads, and she was referred to me by a mutual friend. In our first conversation, I sensed her despair and was disturbed by the dismissive approach of her oncologist and the consulting oncologist at Sloan-Kettering. I had just completed an article for a medical education firm on state-of-the-art chemotherapies for ovarian cancer, and the fact that her Columbia oncologist had tried vinorelbine and adriamycin struck me as strange - these were not the most promising regimens for recurrent and recalcitrant ovarian cancer. Given my doubts about his medical recommendations, I also wondered whether his surgical opinion was also correct. The question of operability was, in my view, a life-and-death issue, since it was exceedingly unlikely that an inoperable tumor that large would be regress sufficiently with any chemotherapy, biotherapy, or alternative treatment to give her a chance for extended survival. I therefore referred Rosemary to the best gynecologic oncologist I knew of, who was also a brilliant surgeon. Peter Dottino, then at Mt. Sinai Medical Center in New York, had a superb reputation, and he also was known as an aggressive chemotherapist in the best sense - he would not give up on patients. He also was open to novel approaches, including cooperative efforts with Dr. Robert Nagourney of Long Beach, California, who utilized a chemotherapy sensitivity assay that I believed was demonstrably helpful in identifying the most promising chemotherapy regimens for a particular individual's tumor. Nagourney's approach was widely rejected by most mainstream oncologists who were not aware of his unique methods or success rates. I encouraged Rosemary to seek a second opinion from Dottino on both chemotherapy and surgery, emphasizing the importance of the surgical question. In essence, I told her that any possibility that her large pelvic tumor could be successfully removed was a risk worth taking given her current circumstances. I openly derided the death sentences of her oncologist and the consulting oncologist at MSKCC and told her that if Dottino did not have a hopeful plan I would continue to work with her until we found an oncologist who offered a serious plan and was willing to fight with and for her. I also told her that once this issue was decided that she could consider a trip to Evanston, Illinois for a consultation with complementary cancer physician Keith Block at the Block Medical Center. Rosemary consulted Dottino and called me afterwards to report on the meeting. He examined her, read her medical records and test results, and studied her most recent CAT scan. To her surprise, he said that he could perform the surgery to remove the pelvic tumor and felt that it would surely benefit her prognosis. She asked whether the necessary plastic surgery would be possible, and Dottino called his collaborating plastic surgeon into his office. This surgeon evaluated Rosemary';s scan and discussed the technical considerations with Dottino, and they both said they thought the procedure was technically feasible, though she would be left with criss-crossing scars. Further, Dottino told her he would follow the surgery with chemotherapy - probably an ifosfamide-based regimen. I was delighted to hear that surgery was possible and believed that an ifosfamide-based regimen made sense, based on response rates recently published. In my conversations with her during this time, I simply offered emotional support, acting as a "healing coach" who cheered her on and reinforced her faith in her physician, who was prepared to go the extra mile to extend her life. Rosemary's surgery occurred several weeks later. During the arduous five-hour procedure, the entire tumor was removed, with no apparent residual cancer in the pelvic region, and the plastic surgery was also successful. Dottino told Rosemary how good he felt the result was, which buoyed her spirits as she recovered from this physically and emotionally demanding event. About six weeks later, she began chemotherapy treatments to treat the lung metastasis and to eradicate any microscopic cancer cells in her lower abdomen. She was followed with CA-125 tests and CAT scans to monitor progress. Her ifosfamide regimen kept her stable (no progression of lung tumors, additional metastates, or rapid rise in CA-125) for several months, after which her CA-125 began to rise. Dottino switched her to a dose-intensive Taxol regimen with similar results: a drop in CA-125 and several months of stable disease followed by an increase in CA-125 and some increased size of lung metastases. One small lymph node in her groin region was also found to be malignant after excision. At this point Dottino decided to send this small tumor sample for analysis by Dr. Nagourney's laboratory, where an EVA (Ex Vivo Apoptotic) chemotherapy sensitivity assay would be performed with over a dozen different agents and combinations tested. Nagourney's report suggested that the combination of a newer agent, Gemcitabine (Gemzar) and cisplatin,would be potentially effective in treating Rosemary's metastatic disease; this combination showed the highest efficacy and the two agents showed evidence of synergy. During this time, with my encouragement Rosemary went to the Block Medical Center where she met with Dr. Block and his associates. She began his low-fat diet replete with phytonutrients and took the supplements he recommended: antioxidants, botanicals, minerals, vitamins, amino acids, and other nutrients with anti-cancer properties that would also work synergistically with chemotherapy and reduce the severity of her side effects. She was motivated by the Block team, with my support, to engage in meditation and exercise. While she had some stomach trouble with the supplements, she did her best to stick with the regimen as she continued to undergo chemotherapy treatments. Rosemary began the Gemzar and cisplatin regimen in late 1997 and it showed evidence of efficacy after the 3rd or 4th treatment. Her CA-125 went down from 500 to slightly under 100, and her lung metasteses stopped growing. After several more treatments, her CA-125 dropped to 45, near normal, and her lung metastases showed some evidence of reduction. While the treatments left her exhausted for several days afterwards, she invariably regained her energy, which was helped by the psychological boost she got from the positive medical results. She began working on new plays, and spent quality time with her husband and daughter, who was now 10 years old. I continued to speak with Rosemary regularly and meet with her every few months. I would support her commitment to the Block regimen and offered occasional adjustments, adding an herbal medicine (i.e., astragulus for immune buttressing, siberian ginseng for energy, etc.) or discussing experimental treatments in clinical trial, such as a E1A gene therapy protocol at MD Anderson in Houston. Meanwhile she continued her Gemzar and cisplatin treatments, and her CA-125 remained near normal while her lung metastastes remained at their reduced size. We talked about her participation in Gilda's Club in New York City, where she attended regular support and meditation groups. One Friday night I attended a performance at Gilda's of a wonderful short play she had written about her chemotherapy and hospital experiences. Rosemary remained healthy and stable for several years while continuing intermittently with Gemzar and cisplatin. During this time her spirits were good and she and I continued to investigate alternatives should her disease progress. I felt this was important for her mind-body health; even if we didn't find a potential magic bullet it kept Rosemary in a hopeful frame of mind. She kept writing, staging several plays, working with actors, spending time with her family. In late 1999 her CA-125 began to rise and her lung masses began to grow. Dr. Dottino made adjustments and additions to her Gemzar/cisplatin regimen while we feverishly pursued new approaches. Her problem was the lung tumors, and I found out about a clinical trial at MD Anderson of a camptothecin chemotherapy drug (9-AC) that could be inhaled to deliver the agent directly to the lungs with fewer systemic side effects and potential for local control. But her condition deteriorated rapidly and her breathing was so labored that she no longer met the eligibility criteria for the study. Indeed, almost all the clinical trials we investigated precluded her enrollment because she had had so many prior chemotherapy regimens or because her Karnovsky performance status was too poor. Rosemary died in February 2000, almost five years after she had been given a death sentence of 3-6 months. She came up 10 months short of realizing her dream of seeing her daughter's Bat Mitzah, but she had those five years to nurture her daughter's development, be with her family, and realize her creativity. I attended her funeral, which was packed with 400 people; her life was celebrated by seven different eulogies by family, friends, and creative partners from the theatre.