Intensive chemo for ovarian cancer

Many patients with ovarian cancer are diagnosed at stage III and IV.   Unfortunately, the cure rate is around 30-40%.   The standard chemo is usually carboplatin and paclitaxel (Taxol) every 3 weeks intravenously.   Some selected patients may receive cisplatin and paclitaxel intraperiteneally (inside abdomen).

A Japanese randomized trial compared the standard carbo+taxol every 3 weeks with an intensive dose regimen and showed a better cure rate.  The Dose-dense treatment: Carboplatin (AUC 6 on day 1) and weekly paclitaxel (80 mg/m² days 1, 8, and 15) every three weeks for six cycles.  This Japanese study was summarized from Uptodate article:

1.       Improvement in median progression free survival (28 versus 17 months; hazard ratio for recurrence [HR] 0.71, 95% CI 0.58-0.88).  PFS means the duration of time from completion of chemo to the recurrence of cancer.

2. Significant improvement in overall survival at three years (HR for mortality 0.75, 95% CI 0.57-0.98).
3. A higher rate of treatment discontinuation for toxicity (52 versus 37 percent) and higher proportion of patients who had at least one treatment cycle delayed because of toxicity (76 versus 67 percent).
4. Similar frequency of severe (grade 3 or 4) nonhematologic toxicity (including neurotoxicity).
5. No difference in rate of febrile neutropenia between groups (9 percent).  Febrile neutropenia means fever due to suppressed immune system.

This new regimen seems to be effective but with higher toxicities.  Do discuss risks and benefits with your oncologist.

REFERENCE

1.      Katsumata N, et al. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009;374(9698):1331.

2.      Uptodate. Herzog T.  accessed 2-24-2013

treatment for recurrence or advanced uterine cancer

Uterine cancer is the most common gynecologic cancer in the United States.  In 2013, 49,000 women is estimated to develop this cancer.  We think many of these cancers are related to obesity.

Fortunately, many patients are cured with hysterectomy surgery.  However, about 20 percent will have advanced cancer and ofter recurred.   We thought that we ought to treat these patients aggressively.   Thus, Cisplatin, doxorubicin, plus paclitaxel regimen was promoted based on GOG 177, which enrolled 273 women with previously untreated stage III/IV or recurrent endometrial cancer and randomized them to treatment with Cisplatin+Doxorubicin vs Taxol+Adriamycin (or Doxorubicin)+Platinum (Cisplatin).  The study showed better survival with TAP (15 months) vs CD (12 months).  However, TAP is very toxic especially with neuropathy.   Thus, another study (GOG 209) compared carbo+taxol vs TAP.   Carbo+taxol seems to be equally effective as TAP with less toxicities:  sensory neuropathy (19 versus 26 percent), thrombocytopenia (12 versus 23 percent), emesis (4 versus 7 percent), diarrhea (2 versus 6 percent), and metabolic derangements (8 versus 14 percent). 

Thus, the studies suggest that patients with advanced or recurrent uterine cancer should receive carbo+taxol.

Reference:

Fleming GF, et al.  Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2004;22(11):2159.  GOG 177

Miller DS, Filiaci G, Mannel R, et al. Randomized Phase III Noninferiority Trial of First Line Chemotherapy for Metastatic or Recurrent Endometrial Carcinoma: A Gynecologic Oncology Group Study. LBA2. Presented at the 2012 Society of Gynecologic Oncology Annual Meeting, Austin, TX.  GOG 209

Coffe after surgery?

Most patients usually experience "sleepy bowel" after surgery.  Doctors call this postoperative ileus.   The symptoms usually are low appetite, nausea after eating, sometimes vomiting and delayed bowel movement. 

 

Muller randomized 80 patients into two groups: one group were fed water and the other were fed coffe after abdominal/laparascopic surgery.  The patients who drank coffe seemed to resolved their postoperative ileus sooner.  After drinking coffe, they tolerate solid food in 49 hours vs 56 hours who drank water.  The time to tolerance of solid food (49·2(21·3) versus 55·8(30·0) h; P = 0·276) and time to first flatus (40·6(16·1) versus 46·4(20·1) h; P = 0·214) showed a similar trend, but the differences were not significant. Length of hospital stay (10·8(4·4) versus 11·3(4·5) days; P = 0·497)

 

It is an interesting study but I don't usually have patient staying 10 to 11 days in hospital after surgery.

 

Reference:

Muller SA, et al.  Randomized clinical trial on the effect of coffee on postoperative ileus following elective colectomy.  Br J Surg. 2012 Nov;99(11):1530-8. Epub 2012 Sep 14.

 

 

New drug for sarcoma

Sarcoma is a type of aggressive cancer.   In my practice, uterine smooth muscle sarcoma (leiomyosarcoma) is one of the most difficult cancers to cure.   After the hysterectomy, patients are usually given Docetaxel + Gemcitabine chemotherapy.  Many patients then developed recurrence of cancer and be treated with Doxorubicin.  Since many of these patients have cancer recurrence again, oncologist dont have more effective treatment.

Recently, Pazopanib, a multitargeted tyrosine kinase inhibitor, seems to be a potential new drug for this aggressive uterine sarcoma.  van der Graaf randomized 369 patients into Pazopanib vs placebo.  The study showed median progression-free survival was 4·6 months (95% CI 3·7-4·8) for pazopanib compared with 1·6 months (0·9-1·8) for placebo (hazard ratio [HR]0·31, 95% CI 0·24-0·40; p<0·0001). Overall survival was 12·5 months (10·6-14·8) with pazopanib versus 10·7 months (8·7-12·8) with placebo (HR 0·86, 0·67-1·11; p=0·25). The most common adverse events were fatigue (60 in the placebo group [49%]vs 155 in the pazopanib group [65%]), diarrhoea (20 [16%]vs 138 [58%]), nausea (34 [28%]vs 129 [54%]), weight loss (25 [20%]vs 115 [48%]), and hypertension (8 [7%]vs 99 [41%]).

In english as I understood, Pazopanib gives 3 months of free cancer than placebo.  Unfortunately, there were no difference in cure rate between Pazopanib vs placebo.

Reference:

van der Graff WT, et al.  Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012;379(9829):1879.